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Evolutionary and ecological insights into the emergence of arthropod-borne viruses
Accepted Manuscript Title: Evolutionary and ecological insights into the emergence of arthropod-borne viruses Authors: Marco Marklewitz, Sandra Junglen PII: DOI: Reference:
S0001-706X(18)30664-8 https://doi.org/10.1016/j.actatropica.2018.10.006 ACTROP 4805
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Acta Tropica
Received date: Revised date: Accepted date:
24-5-2018 19-9-2018 12-10-2018
Please cite this article as: Marklewitz M, Junglen S, Evolutionary and ecological insights into the emergence of arthropod-borne viruses, Acta Tropica (2018), https://doi.org/10.1016/j.actatropica.2018.10.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Evolutionary and ecological insights into the emergence of arthropod-borne viruses Marco Marklewitz1,2 & Sandra Junglen1,2
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Charité – Universitätsmedizin Berlin, corporate member of Free University Berlin, Humboldt-
University Berlin, and Berlin Institute of Health, Germany; 2German Center for Infection Research
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(DZIF), Germany
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Address for correspondence:
Sandra Junglen, Institute of Virology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin,
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Germany, Tel.: +49-30-450-525477, Fax: +49 (0)30 – 450 525 907, e-mail: [email protected]
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Abstract
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The emergence of arthropod-borne viruses (arboviruses) is of global concern as they can rapidly spread across countries and to new continents as the recent examples of chikungunya virus and Zika virus
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have demonstrated. Whereas the global movement patterns of emerging arboviruses are
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comparatively well studied, there is little knowledge on initial emergence processes that enable sylvatic (enzootic) viruses to leave their natural amplification cycle and infect humans or livestock,
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often also involving infection of anthropophilic vector species. Emerging arboviruses almost exclusively originate in highly biodiverse ecosystems of tropical countries. Changes in host population diversity and density can affect pathogen transmission patterns and are likely to influence arbovirus emergence
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processes. This review focuses on concepts from disease ecology, explaining the interplay between biodiversity and pathogen emergence. Keywords: arbovirus, mosquito, virus evolution, pathogen emergence, virus ecology
1. Introduction Members of the non-taxonomic group of arthropod-borne viruses (arboviruses) are naturally cycling between haematophagous arthropod vectors, such as ticks and mosquitoes, and susceptible vertebrate hosts. Arboviruses have been responsible for numerous outbreaks in humans and significant losses in livestock. Arthropod-borne outbreaks regularly occur in endemic regions, affecting
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millions of people per year, e.g., Dengue virus outbreaks in tropical and subtropical regions of South America and Asia (Bhatt et al., 2012). Of additional concern are outbreaks either caused by known
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arboviruses that have adapted to new vectors and spread to new geographic regions, e.g., chikungunya virus (CHIKV) and Zika virus (ZIKV), or by previously unknown arboviruses that suddenly infected
humans or livestock, e.g., SFTS virus and Schmallenberg virus (Liu et al., 2014; Roth et al., 2014; Weaver
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and Lecuit, 2015; Wernike et al., 2014). In recent years there has been an alarming upsurge in
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arthropod-borne infections, mainly caused by arboviruses that spread to new geographic regions over
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long distances. The rapid and extensive spread is mainly due to increases in host population density,
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global travel, and transportation of goods (Gould et al., 2017; Musso et al., 2018; Paixão et al., 2017; Randolph and Rogers, 2010). Factors contributing to the geographic spread of emerging arboviruses
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have been intensively studied and are comparatively well understood. For example, yellow fever virus
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(YFV) and Dengue virus (DENV), together with the domesticated form of Aedes aegypti, were most likely introduced to the Americas via slave ships coming from Africa (Brown et al., 2014; Bryant et al.,
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2007; Gould et al., 2003; Moureau et al., 2015; Powell and Tabachnick, 2013; Tabachnick, 1991). Sylvatic DENV cycles have been detected in Asia and West Africa and it is unclear whether DENV originated in Africa or Asia (Holmes and Twiddy, 2003; Vasilakis et al., 2011). West Nile virus (WNV)
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was most likely carried from Africa to North America on an airplane either by an infected human or mosquito (Gould et al., 2003; Lanciotti et al., 1999). One of the best-understood examples is the geographic spread of CHIKV. CHIKV was first detected in Tanzania in 1952 (Robinson, 1955). Sporadic outbreaks and epidemics have been reported in the following decades in Africa and Southeast-Asia. The recent global spread of the East/Central/South African (ECSA) lineage of CHIKV from the coast of Kenya in 2004 across the Indian Ocean Islands to India, Southeast Asia, and parts of Europe was linked
to a single sequence change in the viral envelope protein (E1:A226V) that caused increased transmission by the invasive vector Aedes albopictus (Chen et al., 2016; Tsetsarkin et al., 2007). Subsequent several second-step adaptive sequence changes provided additional fitness gains and caused rapid lineage diversification (Tsetsarkin et al., 2014). In addition, recent studies have shown that mosquito populations differ in their ability to select the E1:A226V sequence change (Vazeille et
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al., 2016). For example, Aedes albopicitus from La Réunion was able to select the E1-A226V sequence change, whereas no effect of this sequence change was found for Ae. albopictus populations from
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Congo and Italy (Fortuna et al., 2018; Vazeille et al., 2016; Vega-Rua et al., 2013).
The emergence of Venezuelan equine encephalitis virus (VEEV) was also linked to sequence changes in the envelope glycoprotein (A. C. Brault et al., 2002). These sequence changes gave rise to increased
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virulence and viremia in equids (Anishchenko et al., 2006; Greene et al., 2005) and enhanced the
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infection of the epidemic vector (Aedes taeniorhynchus) (Aaron C Brault et al., 2002), as well as
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infection of other mosquito species that have not been involved in enzootic transmission (Weaver et
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al., 2004).
In contrast, studies on the ecological and biological mechanisms driving the initial emergence
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processes of arboviruses from their original enzootic maintenance cycles have been neglected. There
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is also little knowledge of the genetic diversity and ecology of arboviruses in their natural enzootic maintenance cycles, as only solitary enzootic arbovirus isolates are available. As a consequence,
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constraints on and necessities of adaptive evolutionary processes in the initial phase of arbovirus emergence from enzootic cycles are poorly understood. For example, whereas the global emergence of CHIKV from East Africa over Asia to Europe and the
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Americas is well understood (Chen et al., 2016), it is still unclear from where the ECSA lineage started its emergence process before it was first detected on the coast of Kenya in 2004 (Robinson, 1955). More critically, since there is scarce knowledge on the genetic diversity of CHIKV in Africa and as no sylvatic isolate is available, it is unknown if the E1:A226V sequence change was already present in sylvatic CHIKV populations. As a result, we do not know if the initial spread of sylvatic CHIKV variants was facilitated by genetic selection or by ecological mechanisms, e.g., changes in species composition
due to loss of biodiversity. Interestingly, there is evidence that ecological factors may have played regulatory roles, potentially attenuating the emergence of the E1:A226V sequence change (Stapleford et al., 2014). Whereas this sequence change occurred after several days in mosquitoes under experimental conditions, it took several years for it to emerge in nature. Another example that emphasizes the contribution of ecological factors to viral emergence is the absence of WNV outbreaks
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in Central and South America whereas thousands of WNV cases are recorded in North America each year (Elizondo-Quiroga and Elizondo-Quiroga, 2013; Gubler, 2007). Although WNV competent vector
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species and susceptible hosts are present in Central and South America, no human cases have been reported yet. One explanation for this phenomenon is that cross-reacting flaviviruses occur in these
regions and prevent severe WNV infections in humans and animals (Chancey et al., 2015; Elizondo-
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Quiroga and Elizondo-Quiroga, 2013).
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If we want to get a better understanding of the underlying mechanisms driving arbovirus emergence
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from natural maintenance cycles, concepts from disease ecology and community ecology could give
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important insight into how ecosystem diversity, ecosystem services, as well as population diversity and
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density can influence disease transmission dynamics.
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2. Emergence of arboviruses
Host specificity and limitations. The capability of a virus to infect different host species inevitably
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determines its potential for geographic spread: the presence of a virus is ultimately linked to the presence of its host. In particular, the geographic expansion of arboviruses with their unique dual-host tropism is even more complex and is determined by the availability of both host and vector.
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Aside from the physical presence of a susceptible host, the virus must be able to evade the adaptive and innate immune responses of the vertebrate host. Moreover, the virus has to replicate to a sufficient titre in order to successfully infect an arthropod vector during blood-feeding on the infected person. The virus encounters completely different antiviral immune pathways in arthropods, such as RNAi (RNA interference) and the Toll, IMD (immune deficiency), and JAK-STAT (Janus-kinase signal transducer and activator of transcription protein) pathways (Lucas et al., 2013; Palmer et al., 2018). In
general, arbovirus infections in mosquitoes are believed to be mainly asymptomatic, facilitating lifelong persistent infections (Blair, 2011; Forrester et al., 2014). Arboviruses have evolved specific proteins to counteract the antiviral immune responses of the vertebrate and arthropod. For example, the non-structural protein encoded on the small segment (NSs) of bunyaviruses interacts with several cellular proteins of the Type-I interferon pathway in
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vertebrates (Reviewed in Wuerth and Weber, 2016), the NSs of Rift Valley fever phlebovirus (RVFV) blocks the transcription and the export of host mRNAs from the nucleus, while the NSs of SFTS
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phlebovirus is involved in the inhibition of the RIG-I pathway in the cytoplasm (Billecocq et al., 2004;
Qu et al., 2012). As a counter-defense to antiviral RNAi in arthropods, several arthropod-specific viruses have evolved mechanisms to suppress the RNAi response, e.g., Flock House Virus, Drosophila
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C virus, and Culex Y virus encode viral suppressors of RNAi that bind dsRNA and inhibit processing of
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dsRNA into siRNAs (Galiana-Arnoux et al., 2006; Van Rij et al., 2006).
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In addition, various studies have been shown that the microbiota of the arthropod vector has a strong impact on arbovirus infections. Species of the endosymbiont genus Wolbachia have been shown to
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block DENV, YFV, and ZIKV infections in the mosquito vector Aedes aegypti and therefore limit
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transmission to another vertebrate host (Bourtzis et al., 2014; Dutra et al., 2016). Similarly, Enterobacter ludwigii, Pseudomonas rhodesiae, and Vagococcus salmonarium isolated from Aedes
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albopictus have been described as inhibiting La Crosse virus infections in vitro (Dennison et al., 2014). On the other hand microorganisms can also increase the susceptibility of the vector for arbovirus infections: the presence of Serratia odofifera in Aedes aegypti enhances its susceptibility to CHIKV and
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DENV infections (Apte-Deshpande et al., 2014).
Potential effects of climatic change. Environmental temperature, rainfall, and humidity are important factors defining life history traits of arthropod vectors and their ability to transmit pathogens (vector competence). For example, higher temperatures decreased the egg‐laying time of Ae. aegypti (Costa et al., 2010) and reduced the extrinsic incubation period (timeframe between viraemic blood-meal of
the mosquito and the time when that mosquito becomes infectious) of DENV (Focks et al., 2000; Hopp and Foley, 2001). Furthermore, higher temperatures may allow tropical mosquito species to expand to previously temperate zones and reduce the extrinsic incubation period of poikilothermic mosquitoes (Jia et al., 2007; Kunkel et al., 2006; Paz, 2015). Increasing rainfall results in a higher availability of mosquito breeding sites, causing more progeny in respect of number and time (Turell et
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al., 2005). Global climate change is thus expected to influence the abundance and distribution of bloodfeeding vectors and their associated viruses (Paz, 2015; Semenza and Menne, 2009; Shaman et al.,
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2002). However, the complex nature of climate change and arbovirus ecology impedes predictions of climate-driven arbovirus emergence (Descloux et al., 2012; Lafferty and Mordecai, 2016; Rohr et al., 2011).
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Human activities including anthropogenic disturbance are expected to have a much greater impact on
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arbovirus dispersal and prevalence rates than climatic change (Reiter, 2001). The most prominent
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example is the global spread of Aedes albopictus, which was once endemic to South-East Asia but
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became a cosmopolitan via passive transportation of eggs in used tires and lucky bamboo to the tropics worldwide (Hawley et al., 1987; Madon et al., 2002). Today, Aedes albopictus is listed as one on the
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top 100 invasive species, having established populations even in temperate zones of North America
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and Europe (Kraemer et al., 2015). The yellow fever mosquito, Aedes aegypti, is more sensitive to colder temperatures than Aedes albopictus but can tolerate a wider range of temperatures and is one
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of the most widespread mosquito species globally (Brady et al., 2013). Notably, climate change can also have contrary effects on mosquito abundance as some areas are experiencing intense droughts resulting in local declines of mosquito populations due to absence of breeding sites (Williams et al.,
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2016). This could have positive effects on arbovirus infection rates in specific areas.
3. Diversity and evolution of arboviruses Arboviral intrahost diversity. Arboviruses are almost without exception RNA viruses. RNA viruses lack a proofreading mechanism and consequently a genetically diverse population is produced during replication, often referred to as quasispecies (Lauring and Andino, 2010; Nowak, 1992). During the
infection cycle, arboviruses not only need to infect two disparate hosts, the arthropod and the vertebrate, but also different tissues and various cell types (Figure 1). For example, arboviruses enter the midgut following an arthropod bloodmeal on a viraemic vertebrate host (Franz et al., 2015). For a successful transmission to a vertebrate host, the virus has to infect the midgut epithelial cells, the hemocoel, and the salivary glands (Coffey et al., 2013). Low fidelity RNA replication in each infected
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tissue leads to tissue-specific mutational spectra. It is hypothesized that these tissue-specific diverse populations facilitate infection of different tissues, dissemination within the vector, and that they
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sustain a transmission cycle between insects and vertebrates (Coffey et al., 2011; Patterson et al.,
2018). Importantly, only a fraction of the genetically diverse population is transmitted between different tissues within a host, as well as between hosts (Coffey et al., 2013; Forrester et al., 2012).
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Such a situation, where the virus population is severely reduced and loses its genetic diversity, is
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termed a bottleneck. The various bottlenecks the virus experiences during the transmission cycles
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could lead to an increased number of sub-optimally fit viral particles as deleterious mutations
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accumulate. However, several studies have shown that the arbovirus population bottlenecks do not lead to reduced viral fitness nor affect genetic diversity as the viral diversity is restored following
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dissemination, although the timeline for recovery seems to be mosquito-virus pairing specific (Coffey
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et al., 2011; Forrester et al., 2012; Patterson et al., 2018). Generally, arbovirus replication in mosquitoes fosters virus diversification (Brackney et al., 2009; Jerzak
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et al 2009). However, the level of diversification seems to be mosquito species dependent (Grubaugh et al., 2016). Such vector-specific conditions may have great impacts on emergence processes as arboviruses often have to adapt from enzootic to epizootic mosquito species. To our knowledge, there
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is only one study addressing this topic: No difference in genetic diversity of West Nile virus was found between enzootic and bridge vectors (Grubaugh et al., 2016). Further studies investigating the influence of enzootic, bridge, and epizootic vector species on intrahost genetic diversity and selection of minority variants are needed to understand the genetic mechanisms behind arbovirus emergence (Figure 1B).
Evolution of the arboviral dual-host tropism. The dual-host tropism of arboviruses is a paraphyletic trait as different viral families and orders contain arboviruses. The evolutionary origin of arboviruses is unclear as all taxa of interest also contain additional taxa with a monotropism for either vertebrates or arthropods. Assuming that evolution may lead to more complex structures over time, a host monotropism is believed to be more ancient than a dual-host tropism. The fact that arboviruses can
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also be transmitted horizontally and vertically between arthropods gave rise to the hypothesis that arboviruses may have evolved from arthropod-specific viruses (Dudas and Obbard, 2015; Elliott, 2014).
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This hypothesis is supported by the discovery of a large diversity of arthropod-associated viruses that branch deeper than congeneric arboviruses (Cook et al., 2012; Guterres et al., 2017; Li et al., 2015;
Marklewitz et al., 2013, 2011; Shi et al., 2016). Phenotypic analyses of newly discovered insect-specific
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bunyaviruses have shown that none of these viruses were able to infect vertebrate cells nor able to
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replicate at vertebrate-typic temperatures (Marklewitz et al., 2015). These in vitro host range studies
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together with phylogenetic ancestral host reconstructions revealed that the vertebrate-pathogenic
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bunyaviruses evolved from arthropod-specific progenitors (Marklewitz et al., 2015). The ability to infect vertebrates has evolved at least four times in the order Bunyavirales as vertebrate-infecting
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viruses are present in several apical genera. Similar expansions of the host-tropism may also have
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occurred in other families, e.g., in the families Flavi- and Togaviridae, as also discussed above. Vertebrate host restriction of insect-specific viruses has so far been investigated for two viruses only.
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The viruses belong to different virus families, containing important human pathogens: Niénokoué virus (NIEV) in the genus Flavivirus of the family Flaviviridae and Eilat virus (EILV) in the genus Alphavirus of the family Togaviridae. Experimental studies on NIEV using an infectious cDNA clone, a reporter
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replicon, and chimeric YFV carrying the envelope proteins of NIEV revealed that the ability to infect vertebrates involves multiple barriers, including attachment/entry, replication, and assembly/release (Junglen et al., 2017). Interestingly, vertebrate host restriction for EILV was identified at two independent stages of the viral life cycle, at the level of entry and genomic replication using chimeras of the vertebrate pathogenic Sindbis virus and EILV (Nasar et al., 2015, 2012). The fact that similar barriers of insect-specific viruses to infect vertebrate hosts have been identified in two different virus
families suggests that the evolution of the host range expansion from insects to vertebrates is highly complex and sudden host range expansions of insect-specific viruses to vertebrates are rather unlikely. Within the genus Flavivirus there is an additional group of viruses that has only been detected in vertebrates, almost exclusively in bats and rodents, and is named the no-known-vector flaviviruses. In contrast to insect-specific flaviviruses, no-known-vector flaviviruses display a host-range restriction to
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vertebrates and are not able to infect mosquito or tick cells, e.g., Rio Bravo virus or Modoc virus (MODV) (Hendricks et al., 1983; Lawrie et al., 2004; Leyssen et al., 2002). Interestingly, the inability of
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no-known-vector flaviviruses to infect arthropods occurs at a post-entry stage as chimeras of DENV and YFV carrying each the envelope proteins of MODV productively infected mosquito cells but transfected MODV RNA itself did not (Charlier et al., 2010). These studies on host-range restriction of
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insect-specific flaviviruses and no-known-vector flaviviruses suggest that the latter have fewer host-
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range restriction barriers as the first step of the viral life cycle, entry/attachment, does not represent
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a barrier.
Influence of ecosystem modification on arboviruses. Primary ecosystems contain an exceptional
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diversity of animals and plants (Gibson et al., 2011; Myers et al., 2000). Nearly one-third of all known
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species are threatened with extinction due to ecosystems modification and habitat loss (IUCN, 2018). There is growing evidence that the loss of biodiversity alters pathogen transmission patterns (Keesing
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et al., 2010a, 2006a). Given the dramatic global environmental change and the unparalleled loss of biodiversity (Barnosky et al., 2011; Wake and Vredenburg, 2008), there is an urgent need to understand ecological mechanisms driving pathogen emergence.
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Hypotheses trying to explain the linkages between ecosystem modification and the upsurge in infectious diseases are coming from the fields of disease ecology and community ecology. There are currently three main hypotheses that are to some extent controversial (Figure 1A). The most widely accepted is the dilution effect hypothesis, which assumes that a high species diversity reduces the spread of pathogens by diluting the density of susceptible hosts for the pathogen of interest (Civitello et al., 2015; Cohen et al., 2016; Keesing et al., 2010a, 2006b; Pagán et al., 2012). Loss of biodiversity
can be advantageous for certain hosts (generalists) and amplifies their respective pathogens. In a nutshell, high biodiversity has a protective effect on infectious disease. Accordingly, the dilution effect aims at explaining differences in infection rates of (epidemic) pathogens that are able to infect humans and livestock. Numerous studies have shown that high biodiversity reduces pathogen transmission and infection rates in humans, wildlife, livestock, and plants (Begon et al., 2009; Civitello et al., 2015;
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Ezenwa et al., 2006; Keesing et al., 2010a; Khalil et al., 2016; Lacroix et al., 2013; Ostfeld and Keesing, 2012). The dilution effect hypothesis has so far only been studied for a single arbovirus, WNV. It was
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shown that a higher diversity of birds correlates with lower incidence of human infection in the United States (Allan et al., 2009; Swaddle and Calos, 2008). Another study found higher seroprevalence rates of WNV in birds in areas with a higher bird diversity (Levine et al., 2017). The study area was dominated
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by sub-optimal host species, which may explain the contrary observations. Other studies could also
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not confirm the dilution effect, suggesting that it is not generally applicable (Loss et al., 2009;
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Milholland et al., 2017; Ogden and Tsao, 2009; Wood et al., 2014). However, an increasingly
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widespread view suggests that neutral or contrary effects could occur under specific circumstances (Johnson and Thieltges, 2010; Keesing et al., 2010b, 2006a; Ostfeld and Keesing, 2012; Ostfeld and
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Keesing, 2000a; Ostfeld and Keesing, 2000b; Ostfeld and LoGiudice, 2003; Pongsiri et al., 2009; Schmidt
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and Ostfeld, 2001), but high biodiversity, especially in primary ecosystems, principally reduces pathogen prevalence rates (Cardinale et al., 2012).
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Whereas the dilution effect focuses on infection rates of a single pathogen in a single host, another hypothesis, the amplification effect hypothesis, takes into account that each host in a biodiverse ecosystem is infected with pathogens, thus causing a putative higher overall infection rate due to
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additive effects of pathogen carriage (Faust et al., 2017; Randolph and Dobson, 2012). Briefly, this hypothesis assumes that high host diversity translates into high diversity of pathogens (Randolph and Dobson, 2012). The idea of the amplification effect mainly arises from empirical studies and data from field experiments or natural populations is difficult to find. A third hypothesis, the intermediate disturbance hypothesis, predicts that local species diversity is maximized at intermediate intensity of disturbance (Molino and Sabatier, 2001). According to this
hypothesis, disturbance acts as a driver of diversity as it disrupts stable ecosystems and can induce movement of species from adjacent non-disturbed and highly disturbed ecosystems. However, studies have shown that the intermediate disturbance hypothesis is not broadly applicable to organisms and communities (Bongers et al., 2009; Fox, 2013). A recent study on the interplay between forest disturbance and mosquito species composition in Panama could not confirm the intermediate
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disturbance hypothesis as the highest diversity of mosquito species was found in old-growth forests (Loaiza et al., 2017). Notably, linkages between the intermediate disturbance hypothesis and infectious
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disease have not been explored yet.
The conflicting hypotheses and conflicting patterns of empirical data underline that more studies are needed to understand how biodiversity affects pathogen prevalence and infection risk. In particular,
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the effects of host-related factors, such as mobility, lifespan, and density, on prevalence patterns of
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specific pathogens need to be investigated. Studies in population ecology are generally performed
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within single host and single pathogen systems. However, to identify the underlying processes
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are of paramount importance.
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controlling infection risk, studies on multi-host and multi pathogen systems in natural communities
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4. Conclusions
Arboviruses are of the greatest importance for human and animal health worldwide. Multiple
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arboviruses have emerged in the recent past and caused epidemics of global concern. Knowledge of the mechanisms driving the emergence of viruses from their natural maintenance cycles to infect livestock and humans is still very limited. Enlightening studies are coming from the field of community
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ecology. However, studies have mainly focused on bacterial and parasitic pathogens and publications on viral infections are limited to single-host single-pathogen relationships. Studies of mosquito population compositions and patterns of viral infection in different ecosystems could help to identify critical factors fostering arbovirus emergence.
Acknowledgements
This work was funded by the Federal Ministry of Education and Research (BMBF) under project number 01KI1716 as part of the Research Network Zoonotic Infectious Diseases.
5. References Allan, B.F., Langerhans, R.B., Ryberg, W.A., Landesman, W.J., Griffin, N.W., Katz, R.S., Oberle, B.J.,
IP T
Schutzenhofer, M.R., Smyth, K.N., De St. Maurice, A., Clark, L., Crooks, K.R., Hernandez, D.E., McLean, R.G., Ostfeld, R.S., Chase, J.M., 2009. Ecological correlates of risk and incidence of
SC R
West Nile virus in the United States. Oecologia. https://doi.org/10.1007/s00442-008-1169-9
Anishchenko, M., Bowen, R.A., Paessler, S., Austgen, L., Greene, I.P., Weaver, S.C., 2006. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation. Proc. Natl.
U
Acad. Sci. 103, 4994–4999. https://doi.org/10.1073/pnas.0509961103
N
Apte-Deshpande, A.D., Paingankar, M.S., Gokhale, M.D., Deobagkar, D.N., 2014. Serratia odorifera
A
mediated enhancement in susceptibility of Aedes aegypti for chikungunya virus. Indian J. Med.
M
Res. 139, 762–768.
Barnosky, A.D., Matzke, N., Tomiya, S., Wogan, G.O.U., Swartz, B., Quental, T.B., Marshall, C.,
ED
McGuire, J.L., Lindsey, E.L., Maguire, K.C., Mersey, B., Ferrer, E.A., 2011. Has the Earth’s sixth
PT
mass extinction already arrived? Nature 471, 51–57. https://doi.org/10.1038/nature09678 Begon, M., Telfer, S., Burthe, S., Lambin, X., Smith, M.J., Paterson, S., 2009. Effects of abundance on
CC E
infection in natural populations: Field voles and cowpox virus. Epidemics 1, 35–46. https://doi.org/10.1016/j.epidem.2008.10.001
Bhatt, S., Gething, P., Brady, O., Messina, J., Farlow, A., Moyes, C., 2012. The global distribution and
A
burden of dengue. NIH-PA Author Manuscr. Nat. https://doi.org/10.1038/nature12060.The
Billecocq, A., Spiegel, M., Vialat, P., Kohl, A., Weber, F., Bouloy, M., Haller, O., 2004. NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription. J. Virol. 78, 9798–806. https://doi.org/10.1128/JVI.78.18.9798-9806.2004 Blair, C.D., 2011. Mosquito RNAi is the major innate immune pathway controlling arbovirus infection and transmission. Future Microbiol. 6, 265–277. https://doi.org/10.2217/fmb.11.11
Bongers, F., Poorter, L., Hawthorne, W.D., Sheil, D., 2009. The intermediate disturbance hypothesis applies to tropical forests, but disturbance contributes little to tree diversity. Ecol. Lett. https://doi.org/10.1111/j.1461-0248.2009.01329.x Bourtzis, K., Dobson, S.L., Xi, Z., Rasgon, J.L., Calvitti, M., Moreira, L. a., Bossin, H.C., Moretti, R., Baton, L.A., Hughes, G.L., Mavingui, P., Gilles, J.R.L., 2014. Harnessing mosquito-Wolbachia
IP T
symbiosis for vector and disease control. Acta Trop. 132, S150–S163. https://doi.org/10.1016/j.actatropica.2013.11.004
SC R
Brault, A.C., Powers, A.M., Holmes, E.C., Woelk, C.H., Weaver, S.C., 2002. Positively Charged Amino Acid Substitutions in the E2 Envelope Glycoprotein Are Associated with the Emergence of
https://doi.org/10.1128/JVI.76.4.1718-1730.2002
U
Venezuelan Equine Encephalitis Virus. J. Virol. 76, 1718–1730.
N
Brault, A.C., Powers, A.M., Weaver, S.C., 2002. Vector infection determinants of Venezuelan equine
A
encephalitis virus reside within the E2 envelope glycoprotein. J. Virol. 76, 6387–6392.
M
https://doi.org/10.1128/JVI.76.12.6387-6392.2002
Brown, J.E., Evans, B.R., Zheng, W., Obas, V., Barrera-Martinez, L., Egizi, A., Zhao, H., Caccone, A.,
ED
Powell, J.R., 2014. Human impacts have shaped historical and recent evolution in Aedes aegypti,
PT
the dengue and yellow fever mosquito. Evolution (N. Y). 68, 514–525. https://doi.org/10.1111/evo.12281
CC E
Bryant, J.E., Holmes, E.C., Barrett, A.D.T., 2007. Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas. PLoS Pathog. 3, e75. https://doi.org/10.1371/journal.ppat.0030075
A
Cardinale, B.J., Duffy, J.E., Gonzalez, A., Hooper, D.U., Perrings, C., Venail, P., Narwani, A., MacE, G.M., Tilman, D., Wardle, D.A., Kinzig, A.P., Daily, G.C., Loreau, M., Grace, J.B., Larigauderie, A., Srivastava, D.S., Naeem, S., 2012. Biodiversity loss and its impact on humanity. Nature. https://doi.org/10.1038/nature11148 Chancey, C., Grinev, A., Volkova, E., Rios, M., 2015. The global ecology and epidemiology of west nile virus. Biomed Res. Int. https://doi.org/10.1155/2015/376230
Charlier, N., Davidson, A., Dallmeier, K., Molenkamp, R., De Clercq, E., Neyts, J., 2010. Replication of not-known-vector flaviviruses in mosquito cells is restricted by intracellular host factors rather than by the viral envelope proteins. J. Gen. Virol. 91, 1693–1697. https://doi.org/10.1099/vir.0.019851-0 Chen, R., Puri, V., Fedorova, N., Lin, D., Hari, K.L., Jain, R., Rodas, J.D., Das, S.R., Shabman, R.S.,
the Global Expansion of Chikungunya Virus. J. Virol. 90, 10600–10611.
SC R
https://doi.org/10.1128/JVI.01166-16
IP T
Weaver, S.C., 2016. Comprehensive Genome Scale Phylogenetic Study Provides New Insights on
Civitello, D.J., Cohen, J., Fatima, H., Halstead, N.T., Liriano, J., McMahon, T.A., Ortega, C.N., Sauer,
dilution effect. Proc. Natl. Acad. Sci. 112, 8667–8671.
N
https://doi.org/10.1073/pnas.1506279112
U
E.L., Sehgal, T., Young, S., Rohr, J.R., 2015. Biodiversity inhibits parasites: Broad evidence for the
A
Coffey, L.L., Beeharry, Y., Borderia, a. V., Blanc, H., Vignuzzi, M., 2011. Arbovirus high fidelity variant
M
loses fitness in mosquitoes and mice. Proc. Natl. Acad. Sci. 108, 16038–16043. https://doi.org/10.1073/pnas.1111650108
ED
Coffey, L.L., Forrester, N., Tsetsarkin, K., Vasilakis, N., Weaver, S.C., 2013. Factors shaping the
PT
adaptive landscape for arboviruses: implications for the emergence of disease. Future Microbiol. 8, 155–176. https://doi.org/10.2217/fmb.12.139
CC E
Cohen, J.M., Civitello, D.J., Brace, A.J., Feichtinger, E.M., Ortega, C.N., Richardson, J.C., Sauer, E.L., Liu, X., Rohr, J.R., 2016. Spatial scale modulates the strength of ecological processes driving disease distributions. Proc. Natl. Acad. Sci. 113, E3359–E3364.
A
https://doi.org/10.1073/pnas.1521657113
Cook, S., Moureau, G., Kitchen, A., Gould, E.A., de Lamballerie, X., Holmes, E.C., Harbach, R.E., 2012. Molecular evolution of the insect-specific flaviviruses. J. Gen. Virol. 93, 223–234. https://doi.org/10.1099/vir.0.036525-0 Costa, E.A.P.D.A., Santos, E.M.D.M., Correia, J.C., Albuquerque, C.M.R. De, 2010. Impact of small variations in temperature and humidity on the reproductive activity and survival of Aedes
aegypti (Diptera, Culicidae). Rev. Bras. Entomol. https://doi.org/10.1590/S008556262010000300021 Dennison, N.J., Jupatanakul, N., Dimopoulos, G., 2014. The mosquito microbiota influences vector competence for human pathogens. Curr. Opin. Insect Sci. 3, 6–13. https://doi.org/10.1016/j.cois.2014.07.004
IP T
Descloux, E., Mangeas, M., Menkes, C.E., Lengaigne, M., Leroy, A., Tehei, T., Guillaumot, L., Teurlai, M., Gourinat, A.C., Benzler, J., Pfannstiel, A., Grangeon, J.P., Degallier, N., de Lamballerie, X.,
Trop. Dis. https://doi.org/10.1371/journal.pntd.0001470
SC R
2012. Climate-based models for understanding and forecasting dengue epidemics. PLoS Negl.
Dudas, G., Obbard, D.J., 2015. Are arthropods at the heart of virus evolution? Elife 2015, 1–3.
U
https://doi.org/10.7554/eLife.05378
N
Dutra, H.L.C., Rocha, M.N., Dias, F.B.S., Mansur, S.B., Caragata, E.P., Moreira, L.A., 2016. Wolbachia
A
Blocks Currently Circulating Zika Virus Isolates in Brazilian Aedes aegypti Mosquitoes. Cell Host
M
Microbe 19, 771–774. https://doi.org/10.1016/j.chom.2016.04.021 Elizondo-Quiroga, D., Elizondo-Quiroga, A., 2013. West Nile virus and its theories, a big puzzle in
ED
Mexico and Latin America. J. Glob. Infect. Dis. https://doi.org/10.4103/0974-777X.122014
PT
Elliott, R.M., 2014. Orthobunyaviruses: recent genetic and structural insights. Nat. Rev. Microbiol. 12, 673–685. https://doi.org/10.1038/nrmicro3332
CC E
Ezenwa, V.O., Godsey, M.S., King, R.J., Guptill, S.C., 2006. Avian diversity and West Nile virus: testing associations between biodiversity and infectious disease risk. Proc. Biol. Sci. https://doi.org/10.1098/rspb.2005.3284
A
Faust, C.L., Dobson, A.P., Gottdenker, N., Bloomfield, L.S.P., McCallum, H.I., Gillespie, T.R., DiukWasser, M., Plowright, R.K., 2017. Null expectations for disease dynamics in shrinking habitat: Dilution or amplification? Philos. Trans. R. Soc. B Biol. Sci. https://doi.org/10.1098/rstb.2016.0173 Focks, D.A., Brenner, R.J., Hayes, J., Daniels, E., 2000. Transmission thresholds for dengue in terms of Aedes aegypti pupae per person with discussion of their utility in source reduction efforts. Am.
J. Trop. Med. Hyg. https://doi.org/10.4269/ajtmh.2000.62.11 Forrester, N.L., Coffey, L.L., Weaver, S.C., 2014. Arboviral bottlenecks and challenges to maintaining diversity and fitness during mosquito transmission. Viruses. https://doi.org/10.3390/v6103991 Forrester, N.L., Guerbois, M., Seymour, R.L., Spratt, H., Weaver, S.C., 2012. Vector-Borne Transmission Imposes a Severe Bottleneck on an RNA Virus Population. PLoS Pathog. 8.
IP T
https://doi.org/10.1371/journal.ppat.1002897 Fortuna, C., Toma, L., Remoli, M.E., Amendola, A., Severini, F., Boccolini, D., Romi, R., Venturi, G.,
SC R
Rezza, G., Di Luca, M., 2018. Vector competence of Aedes albopictus for the Indian Ocean lineage (IOL) chikungunya viruses of the 2007 and 2017 outbreaks in Italy: a comparison
between strains with and without the E1:A226V mutation. Euro Surveill. Bull. Eur. sur les Mal.
U
Transm. = Eur. Commun. Dis. Bull. 23. https://doi.org/10.2807/1560-
N
7917.ES.2018.23.22.1800246
M
https://doi.org/10.1016/j.tree.2012.08.014
A
Fox, J.W., 2013. The intermediate disturbance hypothesis should be abandoned. Trends Ecol. Evol.
Franz, A.W.E., Kantor, A.M., Passarelli, A.L., Clem, R.J., 2015. Tissue barriers to arbovirus infection in
ED
mosquitoes. Viruses. https://doi.org/10.3390/v7072795
PT
Galiana-Arnoux, D., Dostert, C., Schneemann, A., Hoffmann, J.A., Imler, J.L., 2006. Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat. Immunol.
CC E
https://doi.org/10.1038/ni1335 Gibson, L., Lee, T.M., Koh, L.P., Brook, B.W., Gardner, T. a., Barlow, J., Peres, C. a., Bradshaw, C.J. a., Laurance, W.F., Lovejoy, T.E., Sodhi, N.S., 2011. Primary forests are irreplaceable for sustaining
A
tropical biodiversity. Nature 478, 378–381. https://doi.org/10.1038/nature10425
Gould, E. a, de Lamballerie, X., Zanotto, P.M.A., Holmes, E.C., 2003. Origins, evolution, and vector/host coadaptations within the genus Flavivirus. Adv. Virus Res. 59, 277–314. https://doi.org/10.1016/S0065-3527(03)59008-X Gould, E., Pettersson, J., Higgs, S., Charrel, R., de Lamballerie, X., 2017. Emerging arboviruses: Why today? One Heal. 4, 1–13. https://doi.org/10.1016/j.onehlt.2017.06.001
Greene, I.P., Paessler, S., Austgen, L., Anishchenko, M., Brault, A.C., Bowen, R.A., Weaver, S.C., 2005. Envelope Glycoprotein Mutations Mediate Equine Amplification and Virulence of Epizootic Venezuelan Equine Encephalitis Virus. J. Virol. 79, 9128–9133. https://doi.org/10.1128/JVI.79.14.9128-9133.2005 Grubaugh, N.D., Weger-Lucarelli, J., Murrieta, R.A., Fauver, J.R., Garcia-Luna, S.M., Prasad, A.N.,
IP T
Black, W.C., Ebel, G.D., 2016. Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching. Cell Host Microbe 19, 481–
SC R
492. https://doi.org/10.1016/j.chom.2016.03.002
Gubler, D.J., 2007. The Continuing Spread of West Nile Virus in the Western Hemisphere. Clin. Infect. Dis. 45, 1039–1046. https://doi.org/10.1086/521911
U
Guterres, A., de Oliveira, R.C., Fernandes, J., de Lemos, E.R.S., Schrago, C.G., 2017. New bunya-like
A
https://doi.org/10.1016/j.meegid.2017.01.019
N
viruses: Highlighting their relations. Infect. Genet. Evol. 49, 164–173.
M
Hendricks, D.A., Hardy, J.L., Reeves, W.C., 1983. Comparison of biological properties of St. Louis encephalitis and Rio bravo viruses. Am. J. Trop. Med. Hyg. 32, 602–609.
ED
Holmes, E.C., Twiddy, S.S., 2003. The origin, emergence and evolutionary genetics of dengue virus.
PT
Infect. Genet. Evol. https://doi.org/10.1016/S1567-1348(03)00004-2 Hopp, M.J., Foley, J.A., 2001. Global-scale relationships between climate and the dengue fever
CC E
vector, Aedes aegypti. Clim. Change. https://doi.org/10.1023/A:1010717502442 IUCN, 2018. The IUCN Red List of Threatened Species [WWW Document]. URL www.IUCNredlist.org (accessed 9.17.18).
A
Jia, Y., Moudy, R.M., Dupuis, A.P., Ngo, K.A., Maffei, J.G., Jerzak, G.V.S., Franke, M.A., Kauffman, E.B., Kramer, L.D., 2007. Characterization of a small plaque variant of West Nile virus isolated in New York in 2000. Virology. https://doi.org/10.1016/j.virol.2007.06.008 Johnson, P.T.J., Thieltges, D.W., 2010. Diversity, decoys and the dilution effect: how ecological communities affect disease risk. J. Exp. Biol. 213, 961–970. https://doi.org/10.1242/jeb.037721 Junglen, S., Korries, M., Grasse, W., Wieseler, J., Kopp, A., Hermanns, K., León-Juárez, M., Drosten, C.,
Kümmerer, B.M., 2017. Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle. mSphere 2, e00375-16. https://doi.org/10.1128/mSphere.0037516 Keesing, F., Belden, L.K., Daszak, P., Dobson, A., Harvell, C.D., Holt, R.D., Hudson, P., Jolles, A., Jones, K.E., Mitchell, C.E., Myers, S.S., Bogich, T., Ostfeld, R.S., 2010a. Impacts of biodiversity on the
IP T
emergence and transmission of infectious diseases. Nature 468, 647–652. https://doi.org/10.1038/nature09575
SC R
Keesing, F., Belden, L.K., Daszak, P., Dobson, A., Harvell, C.D., Holt, R.D., Hudson, P., Jolles, A., Jones, K.E., Mitchell, C.E., Myers, S.S., Bogich, T., Ostfeld, R.S., 2010b. Impacts of biodiversity on the emergence and transmission of infectious diseases. Nature.
U
https://doi.org/10.1038/nature09575
N
Keesing, F., Holt, R.D., Ostfeld, R.S., 2006a. Effects of species diversity on disease risk. Ecol. Lett.
A
https://doi.org/10.1111/j.1461-0248.2006.00885.x
M
Keesing, F., Holt, R.D., Ostfeld, R.S., 2006b. Effects of species diversity on disease risk. Ecol. Lett. 9, 485–498. https://doi.org/10.1111/j.1461-0248.2006.00885.x
ED
Khalil, H., Ecke, F., Evander, M., Magnusson, M., Hörnfeldt, B., 2016. Declining ecosystem health and
PT
the dilution effect. Sci. Rep. 6. https://doi.org/10.1038/srep31314 Kunkel, K.E., Novak, R.J., Lampman, R.L., Gu, W., 2006. Modeling the impact of variable climatic
CC E
factors on the crossover of Culex restauns and Culex pipiens (Diptera: Culicidae), vectors of West Nile virus in Illinois. Am. J. Trop. Med. Hyg. https://doi.org/74/1/168 [pii]
Lacroix, C., Jolles, A., Seabloom, E.W., Power, A.G., Mitchell, C.E., Borer, E.T., 2013. Non-random
A
biodiversity loss underlies predictable increases in viral disease prevalence. J. R. Soc. Interface 11, 20130947–20130947. https://doi.org/10.1098/rsif.2013.0947
Lafferty, K.D., Mordecai, E.A., 2016. The rise and fall of infectious disease in a warmer world. F1000Research. https://doi.org/10.12688/f1000research.8766.1 Lanciotti, R.S., Roehrig, J.T., Deubel, V., Smith, J., Parker, M., Steele, K., Crise, B., Volpe, K.E., Crabtree, M.B., Scherret, J.H., Hall, R.A., MacKenzie, J.S., Cropp, C.B., Panigrahy, B., Ostlund, E., Schmitt,
B., Malkinson, M., Banet, C., Weissman, J., Komar, N., Savage, H.M., Stone, W., McNamara, T., Gubler, D.J., 1999. Origin of the West Nile virus responsible for an outbreak of encephalitis in the Northeastern United States. Science (80-. ). 286, 2333–2337. https://doi.org/10.1126/science.286.5448.2333 Lauring, A.S., Andino, R., 2010. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog.
IP T
https://doi.org/10.1371/journal.ppat.1001005 Lawrie, C.H., Uzcátegui, N.Y., Armesto, M., Bell-Sakyi, L., Gould, E.A., 2004. Susceptibility of mosquito
SC R
and tick cell lines to infection with various flaviviruses. Med. Vet. Entomol. 18, 268–274. https://doi.org/10.1111/j.0269-283X.2004.00505.x
Levine, R.S., Hedeen, D.L., Hedeen, M.W., Hamer, G.L., Mead, D.G., Kitron, U.D., 2017. Avian species
N
https://doi.org/10.1186/s13071-017-1999-6
U
diversity and transmission of West Nile virus in Atlanta, Georgia. Parasit. Vectors.
A
Leyssen, P., Charlier, N., Lemey, P., Billoir, F., Vandamme, A.M., De Clercq, E., De Lamballerie, X.,
M
Neyts, J., 2002. Complete genome sequence, taxonomic assignment, and comparative analysis of the untranslated regions of the Modoc virus, a flavivirus with no known vector. Virology 293,
ED
125–140. https://doi.org/10.1006/viro.2001.1241
PT
Li, C.-X., Shi, M., Tian, J.-H., Lin, X.-D., Kang, Y.-J., Chen, L.-J., Qin, X.-C., Xu, J., Holmes, E.C., Zhang, Y.Z., 2015. Unprecedented genomic diversity of RNA viruses in arthropods reveals the ancestry of
CC E
negative-sense RNA viruses. Elife 4, 1–3. https://doi.org/10.7554/eLife.05378 Liu, Q., He, B., Huang, S.Y., Wei, F., Zhu, X.Q., 2014. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis. Lancet Infect. Dis. https://doi.org/10.1016/S1473-
A
3099(14)70718-2
Loaiza, J.R., Dutari, L.C., Rovira, J.R., Sanjur, O.I., Laporta, G.Z., Pecor, J., Foley, D.H., Eastwood, G., Kramer, L.D., Radtke, M., Pongsiri, M., 2017. Disturbance and mosquito diversity in the lowland tropical rainforest of central Panama. Sci. Rep. 7. https://doi.org/10.1038/s41598-017-07476-2 Loss, S.R., Hamer, G.L., Walker, E.D., Ruiz, M.O., Goldberg, T.L., Kitron, U.D., Brawn, J.D., 2009. Avian host community structure and prevalence of West Nile virus in Chicago, Illinois. Oecologia.
https://doi.org/10.1007/s00442-008-1224-6 Lucas, K.J., Myles, K.M., Raikhel, A.S., 2013. Small RNAs: A new frontier in mosquito biology. Trends Parasitol. https://doi.org/10.1016/j.pt.2013.04.003 Marklewitz, M., Handrick, S., Grasse, W., Kurth, A., Lukashev, A., Drosten, C., Ellerbrok, H., Leendertz, F.H., Pauli, G., Junglen, S., 2011. Gouleako Virus Isolated from West African Mosquitoes
IP T
Constitutes a Proposed Novel Genus in the Family Bunyaviridae. J. Virol. 85, 9227–9234. https://doi.org/10.1128/JVI.00230-11
SC R
Marklewitz, M., Zirkel, F., Kurth, A., Drosten, C., Junglen, S., 2015. Evolutionary and phenotypic
analysis of live virus isolates suggests arthropod origin of a pathogenic RNA virus family. Proc. Natl. Acad. Sci. 112, 7536–7541. https://doi.org/10.1073/pnas.1502036112
U
Marklewitz, M., Zirkel, F., Rwego, I.B., Heidemann, H., Trippner, P., Kurth, A., Kallies, R., Briese, T.,
N
Lipkin, W.I., Drosten, C., Gillespie, T.R., Junglen, S., 2013. Discovery of a Unique Novel Clade of
M
https://doi.org/10.1128/JVI.01862-13
A
Mosquito-Associated Bunyaviruses. J. Virol. 87, 12850–12865.
Milholland, M.T., Castro-Arellano, I., Arellano, E., Nava-García, E., Rangel-Altamirano, G., Gonzalez-
ED
Cozatl, F.X., Suzán, G., Schountz, T., González-Padrón, S., Vigueras, A., Rubio, A. V, Maikis, T.J.,
PT
Westrich, B.J., Martinez, J.A., Esteve-Gassent, M.D., Torres, M., Rodriguez-Ruiz, E.R., Hahn, D., Lacher, T.E., 2017. Species Identity Supersedes the Dilution Effect Concerning Hantavirus
CC E
Prevalence at Sites across Texas and México. ILAR J. 58, 401–412. https://doi.org/10.1093/ilar/ily001
Molino, J.-F., Sabatier, D., 2001. Tree Diversity in Tropical Rain Forests: A Validation of the
A
Intermediate Disturbance Hypothesis. Science (80-. ). 294, 1702–1704. https://doi.org/10.1126/science.1060284
Moureau, G., Cook, S., Lemey, P., Nougairede, A., Forrester, N.L., Khasnatinov, M., Charrel, R.N., Firth, A.E., Gould, E.A., De Lamballerie, X., 2015. New insights into flavivirus evolution, taxonomy and biogeographic history, extended by analysis of canonical and alternative coding sequences e0117849. PLoS One 10. https://doi.org/10.1371/journal.pone.0117849
Musso, D., Rodriguez-Morales, A.J., Levi, J.E., Cao-Lormeau, V.M., Gubler, D.J., 2018. Unexpected outbreaks of arbovirus infections: lessons learned from the Pacific and tropical America. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(18)30269-X Myers, N., Mittermeier, R.A., Mittermeier, C.G., da Fonseca, G.A.B., Kent, J., 2000. Biodiversity hotspots for conservation priorities. Nature 403, 853–858. https://doi.org/10.1038/35002501
homologous and heterologous interference. Virology 484, 51–58.
SC R
https://doi.org/10.1016/j.virol.2015.05.009
IP T
Nasar, F., Erasmus, J.H., Haddow, A.D., Tesh, R.B., Weaver, S.C., 2015. Eilat virus induces both
Nasar, F., Palacios, G., Gorchakov, R. V., Guzman, H., Da Rosa, A.P.T., Savji, N., Popov, V.L., Sherman, M.B., Lipkin, W.I., Tesh, R.B., Weaver, S.C., 2012. Eilat virus, a unique alphavirus with host range
U
restricted to insects by RNA replication. Proc. Natl. Acad. Sci. U. S. A. 109, 14622–7.
N
https://doi.org/10.1073/pnas.1204787109
A
Nowak, M.A., 1992. What is a quasispecies? Trends Ecol. Evol. 7, 118–121.
M
https://doi.org/10.1016/0169-5347(92)90145-2
Ogden, N.H., Tsao, J.I., 2009. Biodiversity and Lyme disease: Dilution or amplification? Epidemics.
ED
https://doi.org/10.1016/j.epidem.2009.06.002
PT
Ostfeld, R.S., Keesing, F., 2012. Effects of Host Diversity on Infectious Disease. Annu. Rev. Ecol. Evol. Syst. https://doi.org/10.1146/annurev-ecolsys-102710-145022
CC E
Ostfeld, R.S., Keesing, F., 2000. Biodiversity series: The function of biodiversity in the ecology of vector-borne zoonotic diseases. Can. J. Zool. https://doi.org/10.1139/z00-172
Ostfeld, R.S., Keesing, F., 2000. Biodiversity and disease risk: The case of Lyme disease. Conserv. Biol.
A
https://doi.org/10.1046/j.1523-1739.2000.99014.x
Ostfeld, R.S., LoGiudice, K., 2003. Community disassembly, biodiversity loss, and the erosion of an ecosystem service. Ecology 84, 1421–1427. https://doi.org/10.1890/02-3125 Pagán, I., González-Jara, P., Moreno-Letelier, A., Rodelo-Urrego, M., Fraile, A., Piñero, D., GarcíaArenal, F., 2012. Effect of biodiversity changes in disease risk: Exploring disease emergence in a plant-virus system. PLoS Pathog. 8, 47. https://doi.org/10.1371/journal.ppat.1002796
Paixão, E.S., Teixeira, M.G., Rodrigues, L.C., 2017. Zika, chikungunya and dengue: the causes and threats of new and re-emerging arboviral diseases. BMJ Glob. Heal. https://doi.org/10.1136/bmjgh-2017-000530 Palmer, W.H., Varghese, F.S., Van Rij, R.P., 2018. Natural variation in resistance to virus infection in dipteran insects. Viruses. https://doi.org/10.3390/v10030118
IP T
Patterson, E.I., Khanipov, K., Rojas, M.M., Kautz, T.F., Rockx-Brouwer, D., Golovko, G., Albayrak, L., Fofanov, Y., Forrester, N.L., 2018. Mosquito bottlenecks alter viral mutant swarm in a tissue and
SC R
time-dependent manner with contraction and expansion of variant positions and diversity. Virus Evol. 4. https://doi.org/10.1093/ve/vey001
Paz, S., 2015. Climate change impacts on West Nile virus transmission in a global context. Philos.
U
Trans. R. Soc. B Biol. Sci. https://doi.org/10.1098/rstb.2013.0561
N
Pongsiri, M.J., Roman, J., Ezenwa, V.O., Goldberg, T.L., Koren, H.S., Newbold, S.C., Ostfeld, R.S.,
A
Pattanayak, S.K., Salkeld, D.J., 2009. Biodiversity Loss Affects Global Disease Ecology.
M
Bioscience. https://doi.org/10.1525/bio.2009.59.11.6
Powell, J.R., Tabachnick, W.J., 2013. History of domestication and spread of Aedes aegypti--a review.
ED
Mem. Inst. Oswaldo Cruz. https://doi.org/10.1590/0074-0276130395
PT
Qu, B., Qi, X., Wu, X., Liang, M., Li, C., Cardona, C.J., Xu, W., Tang, F., Li, Z., Wu, B., Powell, K., Wegner, M., Li, D., Xing, Z., 2012. Suppression of the interferon and NF-κB responses by severe fever
CC E
with thrombocytopenia syndrome virus. J. Virol. 86, 8388–8401. https://doi.org/10.1128/JVI.00612-12
Randolph, S.E., Dobson, A.D.M., 2012. Pangloss revisited: A critique of the dilution effect and the
A
biodiversity-buffers-disease paradigm. Parasitology. https://doi.org/10.1017/S0031182012000200
Randolph, S.E., Rogers, D.J., 2010. The arrival, establishment and spread of exotic diseases: patterns and predictions. Nat. Rev. Microbiol. 8, 361–371. https://doi.org/10.1038/nrmicro2336 Reiter, P., 2001. Climate change and mosquito-borne disease. Environ. Health Perspect. https://doi.org/10.2307/3434853
Robinson, M.C., 1955. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features. Trans. R. Soc. Trop. Med. Hyg. 49, 28–32. Rohr, J.R., Dobson, A.P., Johnson, P.T.J., Kilpatrick, A.M., Paull, S.H., Raffel, T.R., Ruiz-Moreno, D., Thomas, M.B., 2011. Frontiers in climate change-disease research. Trends Ecol. Evol. 26, 270– 277. https://doi.org/10.1016/j.tree.2011.03.002
IP T
Roth, A., Mercier, A., Lepers, C., Hoy, D., Duituturaga, S., Benyon, E., Guillaumot, L., Souarès, Y., 2014. Concurrent outbreaks of dengue, chikungunya and zika virus infections – An unprecedented
https://doi.org/10.2807/1560-7917.ES2014.19.41.20929
SC R
epidemic wave of mosquito-borne viruses in the Pacific 2012–2014. Eurosurveillance 19.
Parasitol. https://doi.org/10.1016/j.pt.2017.12.004
U
Rückert, C., Ebel, G.D., 2018. How Do Virus–Mosquito Interactions Lead to Viral Emergence? Trends
N
Schmidt, K.A., Ostfeld, R.S., 2001. Biodiversity and the dilution effect in disease ecology. Ecology.
A
https://doi.org/10.1890/0012-9658(2001)082[0609:BATDEI]2.0.CO;2
M
Semenza, J.C., Menne, B., 2009. Climate change and infectious diseases in Europe. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(09)70104-5
ED
Shaman, J., Stieglitz, M., Stark, C., Le Blancq, S., Cane, M., 2002. Using a dynamic hydrology model to
PT
predict mosquito abundances in flood and swamp water. Emerg. Infect. Dis. https://doi.org/10.3201/eid0801.010049
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Shi, M., Lin, X.D., Tian, J.H., Chen, L.J., Chen, X., Li, C.X., Qin, X.C., Li, J., Cao, J.P., Eden, J.S., Buchmann, J., Wang, W., Xu, J., Holmes, E.C., Zhang, Y.Z., 2016. Redefining the invertebrate RNA virosphere. Nature 540, 539–543. https://doi.org/10.1038/nature20167
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Stapleford, K.A., Coffey, L.L., Lay, S., Bordería, A. V., Duong, V., Isakov, O., Rozen-Gagnon, K., AriasGoeta, C., Blanc, H., Beaucourt, S., Haliloǧlu, T., Schmitt, C., Bonne, I., Ben-Tal, N., Shomron, N., Failloux, A.B., Buchy, P., Vignuzzi, M., 2014. Emergence and transmission of arbovirus evolutionary intermediates with epidemic potential. Cell Host Microbe 15, 706–716. https://doi.org/10.1016/j.chom.2014.05.008 Swaddle, J.P., Calos, S.E., 2008. Increased avian diversity is associated with lower incidence of human
West Nile infection: Observation of the dilution effect. PLoS One 3. https://doi.org/10.1371/journal.pone.0002488 Tabachnick, W.J., 1991. Evolutionary Genetics and Arthropod-borne Disease: The Yellow Fever Mosquito. Am. Entomol. 37, 14–26. Tsetsarkin, K.A., Chen, R., Yun, R., Rossi, S.L., Plante, K.S., Guerbois, M., Forrester, N., Perng, G.C.,
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Sreekumar, E., Leal, G., Huang, J., Mukhopadhyay, S., Weaver, S.C., 2014. Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes
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albopictus mosquitoes. Nat. Commun. 5, 1–14. https://doi.org/10.1038/ncomms5084
Tsetsarkin, K.A., Vanlandingham, D.L., McGee, C.E., Higgs, S., 2007. A single mutation in Chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog.
U
https://doi.org/10.1371/journal.ppat.0030201
N
Turell, M.J., Dohm, D.J., Sardelis, M.R., O’Guinn, M.L., Andreadis, T.G., Blow, J.A., 2005. An update on
A
the potential of North American mosquitoes (Diptera: Culicidae) to transmit West Nile virus. J.
M
Med. Entomol. https://doi.org/10.1093/jmedent/42.1.57 Van Rij, R.P., Saleh, M.C., Berry, B., Foo, C., Houk, A., Antoniewski, C., Andino, R., 2006. The RNA
ED
silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila
PT
melanogaster. Genes Dev. https://doi.org/10.1101/gad.1482006 Vasilakis, N., Cardosa, J., Hanley, K.A., Holmes, E.C., Weaver, S.C., 2011. Fever from the forest:
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Prospects for the continued emergence of sylvatic dengue virus and its impact on public health. Nat. Rev. Microbiol. https://doi.org/10.1038/nrmicro2595
Vazeille, M., Zouache, K., Vega-Rúa, A., Thiberge, J.M., Caro, V., Yébakima, A., Mousson, L.,
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Piorkowski, G., Dauga, C., Vaney, M.C., Manni, M., Gasperi, G., De Lamballerie, X., Failloux, A.B., 2016. Importance of mosquito “quasispecies” in selecting an epidemic arthropod-borne virus. Sci. Rep. 6. https://doi.org/10.1038/srep29564
Vega-Rua, A., Zouache, K., Caro, V., Diancourt, L., Delaunay, P., Grandadam, M., Failloux, A.B., 2013. High Efficiency of Temperate Aedes albopictus to Transmit Chikungunya and Dengue Viruses in the Southeast of France. PLoS One. https://doi.org/10.1371/journal.pone.0059716
Wake, D.B., Vredenburg, V.T., 2008. Are we in the midst of the sixth mass extinction? A view from the world of amphibians. Proc. Natl. Acad. Sci. https://doi.org/10.1073/pnas.0801921105 Weaver, S.C., Ferro, C., Barrera, R., Boshell, J., Navarro, J.C., 2004. Venezuelan Equine Encephalitis. Annu. Rev. Entomol. 49, 141–174. https://doi.org/10.1146/annurev.ento.49.061802.123422 Weaver, S.C., Lecuit, M., 2015. Chikungunya Virus and the Global Spread of a Mosquito-Borne
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Disease. N. Engl. J. Med. 372, 1231–1239. https://doi.org/10.1056/NEJMra1406035 Wernike, K., Conraths, F., Zanella, G., Granzow, H., Gache, K., Schirrmeier, H., Valas, S., Staubach, C.,
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Marianneau, P., Kraatz, F., Höreth-Böntgen, D., Reimann, I., Zientara, S., Beer, M., 2014. Schmallenberg virus-Two years of experiences. Prev. Vet. Med. 116, 423–434. https://doi.org/10.1016/j.prevetmed.2014.03.021
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Wood, C.L., Lafferty, K.D., DeLeo, G., Young, H.S., Hudson, P.J., Kuris, A.M., 2014. Does biodiversity
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protect humans against infectious disease? Ecology. https://doi.org/10.1890/13-1041.1
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https://doi.org/10.3390/v8060174
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Wuerth, J., Weber, F., 2016. Phleboviruses and the Type I Interferon Response. Viruses 8, 174.
Figure 1: Overview of factors contributing to arbovirus emergence. (A) Host abundance and pathogen diversity are illustrated according to different ecological hypothesis. The Dilution Effect Hypothesis (DEH) predicts a negative correlation between biodiversity and disease risk. The Amplification Effect Hypothesis (AEH) assumes a positive correlation between biodiversity and disease risk. The Intermediate Disturbance hypothesis (IDH) predicts the highest biodiversity in an intermediate
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disturbed ecosystem. (B) Arbovirus amplification cycles and spread. (C) Arbovirus dissemination and infection within a mosquito. The magnified area illustrates one of the bottlenecks in more detail
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including antiviral RNAi as an example for generating genetic diversity upon cell infection (modified
after Rückert and Ebel, 2018). Abbreviations are as follows: salivary glands (SG), basal lamina (BL), midgut epithelium (ME), midgut lumen (ML). Different mosquito and virus species are indicated by
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different colours. Genetically different virus variants are indicated by colour shading.
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S0001-706X(18)30664-8 https://doi.org/10.1016/j.actatropica.2018.10.006 ACTROP 4805
To appear in:
Acta Tropica
Received date: Revised date: Accepted date:
24-5-2018 19-9-2018 12-10-2018
Please cite this article as: Marklewitz M, Junglen S, Evolutionary and ecological insights into the emergence of arthropod-borne viruses, Acta Tropica (2018), https://doi.org/10.1016/j.actatropica.2018.10.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Evolutionary and ecological insights into the emergence of arthropod-borne viruses Marco Marklewitz1,2 & Sandra Junglen1,2
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Charité – Universitätsmedizin Berlin, corporate member of Free University Berlin, Humboldt-
University Berlin, and Berlin Institute of Health, Germany; 2German Center for Infection Research
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(DZIF), Germany
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Address for correspondence:
Sandra Junglen, Institute of Virology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin,
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Germany, Tel.: +49-30-450-525477, Fax: +49 (0)30 – 450 525 907, e-mail: [email protected]
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Abstract
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The emergence of arthropod-borne viruses (arboviruses) is of global concern as they can rapidly spread across countries and to new continents as the recent examples of chikungunya virus and Zika virus
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have demonstrated. Whereas the global movement patterns of emerging arboviruses are
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comparatively well studied, there is little knowledge on initial emergence processes that enable sylvatic (enzootic) viruses to leave their natural amplification cycle and infect humans or livestock,
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often also involving infection of anthropophilic vector species. Emerging arboviruses almost exclusively originate in highly biodiverse ecosystems of tropical countries. Changes in host population diversity and density can affect pathogen transmission patterns and are likely to influence arbovirus emergence
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processes. This review focuses on concepts from disease ecology, explaining the interplay between biodiversity and pathogen emergence. Keywords: arbovirus, mosquito, virus evolution, pathogen emergence, virus ecology
1. Introduction Members of the non-taxonomic group of arthropod-borne viruses (arboviruses) are naturally cycling between haematophagous arthropod vectors, such as ticks and mosquitoes, and susceptible vertebrate hosts. Arboviruses have been responsible for numerous outbreaks in humans and significant losses in livestock. Arthropod-borne outbreaks regularly occur in endemic regions, affecting
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millions of people per year, e.g., Dengue virus outbreaks in tropical and subtropical regions of South America and Asia (Bhatt et al., 2012). Of additional concern are outbreaks either caused by known
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arboviruses that have adapted to new vectors and spread to new geographic regions, e.g., chikungunya virus (CHIKV) and Zika virus (ZIKV), or by previously unknown arboviruses that suddenly infected
humans or livestock, e.g., SFTS virus and Schmallenberg virus (Liu et al., 2014; Roth et al., 2014; Weaver
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and Lecuit, 2015; Wernike et al., 2014). In recent years there has been an alarming upsurge in
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arthropod-borne infections, mainly caused by arboviruses that spread to new geographic regions over
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long distances. The rapid and extensive spread is mainly due to increases in host population density,
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global travel, and transportation of goods (Gould et al., 2017; Musso et al., 2018; Paixão et al., 2017; Randolph and Rogers, 2010). Factors contributing to the geographic spread of emerging arboviruses
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have been intensively studied and are comparatively well understood. For example, yellow fever virus
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(YFV) and Dengue virus (DENV), together with the domesticated form of Aedes aegypti, were most likely introduced to the Americas via slave ships coming from Africa (Brown et al., 2014; Bryant et al.,
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2007; Gould et al., 2003; Moureau et al., 2015; Powell and Tabachnick, 2013; Tabachnick, 1991). Sylvatic DENV cycles have been detected in Asia and West Africa and it is unclear whether DENV originated in Africa or Asia (Holmes and Twiddy, 2003; Vasilakis et al., 2011). West Nile virus (WNV)
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was most likely carried from Africa to North America on an airplane either by an infected human or mosquito (Gould et al., 2003; Lanciotti et al., 1999). One of the best-understood examples is the geographic spread of CHIKV. CHIKV was first detected in Tanzania in 1952 (Robinson, 1955). Sporadic outbreaks and epidemics have been reported in the following decades in Africa and Southeast-Asia. The recent global spread of the East/Central/South African (ECSA) lineage of CHIKV from the coast of Kenya in 2004 across the Indian Ocean Islands to India, Southeast Asia, and parts of Europe was linked
to a single sequence change in the viral envelope protein (E1:A226V) that caused increased transmission by the invasive vector Aedes albopictus (Chen et al., 2016; Tsetsarkin et al., 2007). Subsequent several second-step adaptive sequence changes provided additional fitness gains and caused rapid lineage diversification (Tsetsarkin et al., 2014). In addition, recent studies have shown that mosquito populations differ in their ability to select the E1:A226V sequence change (Vazeille et
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al., 2016). For example, Aedes albopicitus from La Réunion was able to select the E1-A226V sequence change, whereas no effect of this sequence change was found for Ae. albopictus populations from
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Congo and Italy (Fortuna et al., 2018; Vazeille et al., 2016; Vega-Rua et al., 2013).
The emergence of Venezuelan equine encephalitis virus (VEEV) was also linked to sequence changes in the envelope glycoprotein (A. C. Brault et al., 2002). These sequence changes gave rise to increased
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virulence and viremia in equids (Anishchenko et al., 2006; Greene et al., 2005) and enhanced the
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infection of the epidemic vector (Aedes taeniorhynchus) (Aaron C Brault et al., 2002), as well as
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infection of other mosquito species that have not been involved in enzootic transmission (Weaver et
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al., 2004).
In contrast, studies on the ecological and biological mechanisms driving the initial emergence
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processes of arboviruses from their original enzootic maintenance cycles have been neglected. There
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is also little knowledge of the genetic diversity and ecology of arboviruses in their natural enzootic maintenance cycles, as only solitary enzootic arbovirus isolates are available. As a consequence,
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constraints on and necessities of adaptive evolutionary processes in the initial phase of arbovirus emergence from enzootic cycles are poorly understood. For example, whereas the global emergence of CHIKV from East Africa over Asia to Europe and the
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Americas is well understood (Chen et al., 2016), it is still unclear from where the ECSA lineage started its emergence process before it was first detected on the coast of Kenya in 2004 (Robinson, 1955). More critically, since there is scarce knowledge on the genetic diversity of CHIKV in Africa and as no sylvatic isolate is available, it is unknown if the E1:A226V sequence change was already present in sylvatic CHIKV populations. As a result, we do not know if the initial spread of sylvatic CHIKV variants was facilitated by genetic selection or by ecological mechanisms, e.g., changes in species composition
due to loss of biodiversity. Interestingly, there is evidence that ecological factors may have played regulatory roles, potentially attenuating the emergence of the E1:A226V sequence change (Stapleford et al., 2014). Whereas this sequence change occurred after several days in mosquitoes under experimental conditions, it took several years for it to emerge in nature. Another example that emphasizes the contribution of ecological factors to viral emergence is the absence of WNV outbreaks
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in Central and South America whereas thousands of WNV cases are recorded in North America each year (Elizondo-Quiroga and Elizondo-Quiroga, 2013; Gubler, 2007). Although WNV competent vector
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species and susceptible hosts are present in Central and South America, no human cases have been reported yet. One explanation for this phenomenon is that cross-reacting flaviviruses occur in these
regions and prevent severe WNV infections in humans and animals (Chancey et al., 2015; Elizondo-
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Quiroga and Elizondo-Quiroga, 2013).
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If we want to get a better understanding of the underlying mechanisms driving arbovirus emergence
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from natural maintenance cycles, concepts from disease ecology and community ecology could give
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important insight into how ecosystem diversity, ecosystem services, as well as population diversity and
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density can influence disease transmission dynamics.
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2. Emergence of arboviruses
Host specificity and limitations. The capability of a virus to infect different host species inevitably
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determines its potential for geographic spread: the presence of a virus is ultimately linked to the presence of its host. In particular, the geographic expansion of arboviruses with their unique dual-host tropism is even more complex and is determined by the availability of both host and vector.
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Aside from the physical presence of a susceptible host, the virus must be able to evade the adaptive and innate immune responses of the vertebrate host. Moreover, the virus has to replicate to a sufficient titre in order to successfully infect an arthropod vector during blood-feeding on the infected person. The virus encounters completely different antiviral immune pathways in arthropods, such as RNAi (RNA interference) and the Toll, IMD (immune deficiency), and JAK-STAT (Janus-kinase signal transducer and activator of transcription protein) pathways (Lucas et al., 2013; Palmer et al., 2018). In
general, arbovirus infections in mosquitoes are believed to be mainly asymptomatic, facilitating lifelong persistent infections (Blair, 2011; Forrester et al., 2014). Arboviruses have evolved specific proteins to counteract the antiviral immune responses of the vertebrate and arthropod. For example, the non-structural protein encoded on the small segment (NSs) of bunyaviruses interacts with several cellular proteins of the Type-I interferon pathway in
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vertebrates (Reviewed in Wuerth and Weber, 2016), the NSs of Rift Valley fever phlebovirus (RVFV) blocks the transcription and the export of host mRNAs from the nucleus, while the NSs of SFTS
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phlebovirus is involved in the inhibition of the RIG-I pathway in the cytoplasm (Billecocq et al., 2004;
Qu et al., 2012). As a counter-defense to antiviral RNAi in arthropods, several arthropod-specific viruses have evolved mechanisms to suppress the RNAi response, e.g., Flock House Virus, Drosophila
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C virus, and Culex Y virus encode viral suppressors of RNAi that bind dsRNA and inhibit processing of
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dsRNA into siRNAs (Galiana-Arnoux et al., 2006; Van Rij et al., 2006).
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In addition, various studies have been shown that the microbiota of the arthropod vector has a strong impact on arbovirus infections. Species of the endosymbiont genus Wolbachia have been shown to
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block DENV, YFV, and ZIKV infections in the mosquito vector Aedes aegypti and therefore limit
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transmission to another vertebrate host (Bourtzis et al., 2014; Dutra et al., 2016). Similarly, Enterobacter ludwigii, Pseudomonas rhodesiae, and Vagococcus salmonarium isolated from Aedes
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albopictus have been described as inhibiting La Crosse virus infections in vitro (Dennison et al., 2014). On the other hand microorganisms can also increase the susceptibility of the vector for arbovirus infections: the presence of Serratia odofifera in Aedes aegypti enhances its susceptibility to CHIKV and
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DENV infections (Apte-Deshpande et al., 2014).
Potential effects of climatic change. Environmental temperature, rainfall, and humidity are important factors defining life history traits of arthropod vectors and their ability to transmit pathogens (vector competence). For example, higher temperatures decreased the egg‐laying time of Ae. aegypti (Costa et al., 2010) and reduced the extrinsic incubation period (timeframe between viraemic blood-meal of
the mosquito and the time when that mosquito becomes infectious) of DENV (Focks et al., 2000; Hopp and Foley, 2001). Furthermore, higher temperatures may allow tropical mosquito species to expand to previously temperate zones and reduce the extrinsic incubation period of poikilothermic mosquitoes (Jia et al., 2007; Kunkel et al., 2006; Paz, 2015). Increasing rainfall results in a higher availability of mosquito breeding sites, causing more progeny in respect of number and time (Turell et
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al., 2005). Global climate change is thus expected to influence the abundance and distribution of bloodfeeding vectors and their associated viruses (Paz, 2015; Semenza and Menne, 2009; Shaman et al.,
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2002). However, the complex nature of climate change and arbovirus ecology impedes predictions of climate-driven arbovirus emergence (Descloux et al., 2012; Lafferty and Mordecai, 2016; Rohr et al., 2011).
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Human activities including anthropogenic disturbance are expected to have a much greater impact on
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arbovirus dispersal and prevalence rates than climatic change (Reiter, 2001). The most prominent
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example is the global spread of Aedes albopictus, which was once endemic to South-East Asia but
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became a cosmopolitan via passive transportation of eggs in used tires and lucky bamboo to the tropics worldwide (Hawley et al., 1987; Madon et al., 2002). Today, Aedes albopictus is listed as one on the
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top 100 invasive species, having established populations even in temperate zones of North America
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and Europe (Kraemer et al., 2015). The yellow fever mosquito, Aedes aegypti, is more sensitive to colder temperatures than Aedes albopictus but can tolerate a wider range of temperatures and is one
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of the most widespread mosquito species globally (Brady et al., 2013). Notably, climate change can also have contrary effects on mosquito abundance as some areas are experiencing intense droughts resulting in local declines of mosquito populations due to absence of breeding sites (Williams et al.,
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2016). This could have positive effects on arbovirus infection rates in specific areas.
3. Diversity and evolution of arboviruses Arboviral intrahost diversity. Arboviruses are almost without exception RNA viruses. RNA viruses lack a proofreading mechanism and consequently a genetically diverse population is produced during replication, often referred to as quasispecies (Lauring and Andino, 2010; Nowak, 1992). During the
infection cycle, arboviruses not only need to infect two disparate hosts, the arthropod and the vertebrate, but also different tissues and various cell types (Figure 1). For example, arboviruses enter the midgut following an arthropod bloodmeal on a viraemic vertebrate host (Franz et al., 2015). For a successful transmission to a vertebrate host, the virus has to infect the midgut epithelial cells, the hemocoel, and the salivary glands (Coffey et al., 2013). Low fidelity RNA replication in each infected
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tissue leads to tissue-specific mutational spectra. It is hypothesized that these tissue-specific diverse populations facilitate infection of different tissues, dissemination within the vector, and that they
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sustain a transmission cycle between insects and vertebrates (Coffey et al., 2011; Patterson et al.,
2018). Importantly, only a fraction of the genetically diverse population is transmitted between different tissues within a host, as well as between hosts (Coffey et al., 2013; Forrester et al., 2012).
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Such a situation, where the virus population is severely reduced and loses its genetic diversity, is
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termed a bottleneck. The various bottlenecks the virus experiences during the transmission cycles
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could lead to an increased number of sub-optimally fit viral particles as deleterious mutations
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accumulate. However, several studies have shown that the arbovirus population bottlenecks do not lead to reduced viral fitness nor affect genetic diversity as the viral diversity is restored following
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dissemination, although the timeline for recovery seems to be mosquito-virus pairing specific (Coffey
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et al., 2011; Forrester et al., 2012; Patterson et al., 2018). Generally, arbovirus replication in mosquitoes fosters virus diversification (Brackney et al., 2009; Jerzak
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et al 2009). However, the level of diversification seems to be mosquito species dependent (Grubaugh et al., 2016). Such vector-specific conditions may have great impacts on emergence processes as arboviruses often have to adapt from enzootic to epizootic mosquito species. To our knowledge, there
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is only one study addressing this topic: No difference in genetic diversity of West Nile virus was found between enzootic and bridge vectors (Grubaugh et al., 2016). Further studies investigating the influence of enzootic, bridge, and epizootic vector species on intrahost genetic diversity and selection of minority variants are needed to understand the genetic mechanisms behind arbovirus emergence (Figure 1B).
Evolution of the arboviral dual-host tropism. The dual-host tropism of arboviruses is a paraphyletic trait as different viral families and orders contain arboviruses. The evolutionary origin of arboviruses is unclear as all taxa of interest also contain additional taxa with a monotropism for either vertebrates or arthropods. Assuming that evolution may lead to more complex structures over time, a host monotropism is believed to be more ancient than a dual-host tropism. The fact that arboviruses can
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also be transmitted horizontally and vertically between arthropods gave rise to the hypothesis that arboviruses may have evolved from arthropod-specific viruses (Dudas and Obbard, 2015; Elliott, 2014).
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This hypothesis is supported by the discovery of a large diversity of arthropod-associated viruses that branch deeper than congeneric arboviruses (Cook et al., 2012; Guterres et al., 2017; Li et al., 2015;
Marklewitz et al., 2013, 2011; Shi et al., 2016). Phenotypic analyses of newly discovered insect-specific
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bunyaviruses have shown that none of these viruses were able to infect vertebrate cells nor able to
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replicate at vertebrate-typic temperatures (Marklewitz et al., 2015). These in vitro host range studies
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together with phylogenetic ancestral host reconstructions revealed that the vertebrate-pathogenic
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bunyaviruses evolved from arthropod-specific progenitors (Marklewitz et al., 2015). The ability to infect vertebrates has evolved at least four times in the order Bunyavirales as vertebrate-infecting
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viruses are present in several apical genera. Similar expansions of the host-tropism may also have
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occurred in other families, e.g., in the families Flavi- and Togaviridae, as also discussed above. Vertebrate host restriction of insect-specific viruses has so far been investigated for two viruses only.
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The viruses belong to different virus families, containing important human pathogens: Niénokoué virus (NIEV) in the genus Flavivirus of the family Flaviviridae and Eilat virus (EILV) in the genus Alphavirus of the family Togaviridae. Experimental studies on NIEV using an infectious cDNA clone, a reporter
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replicon, and chimeric YFV carrying the envelope proteins of NIEV revealed that the ability to infect vertebrates involves multiple barriers, including attachment/entry, replication, and assembly/release (Junglen et al., 2017). Interestingly, vertebrate host restriction for EILV was identified at two independent stages of the viral life cycle, at the level of entry and genomic replication using chimeras of the vertebrate pathogenic Sindbis virus and EILV (Nasar et al., 2015, 2012). The fact that similar barriers of insect-specific viruses to infect vertebrate hosts have been identified in two different virus
families suggests that the evolution of the host range expansion from insects to vertebrates is highly complex and sudden host range expansions of insect-specific viruses to vertebrates are rather unlikely. Within the genus Flavivirus there is an additional group of viruses that has only been detected in vertebrates, almost exclusively in bats and rodents, and is named the no-known-vector flaviviruses. In contrast to insect-specific flaviviruses, no-known-vector flaviviruses display a host-range restriction to
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vertebrates and are not able to infect mosquito or tick cells, e.g., Rio Bravo virus or Modoc virus (MODV) (Hendricks et al., 1983; Lawrie et al., 2004; Leyssen et al., 2002). Interestingly, the inability of
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no-known-vector flaviviruses to infect arthropods occurs at a post-entry stage as chimeras of DENV and YFV carrying each the envelope proteins of MODV productively infected mosquito cells but transfected MODV RNA itself did not (Charlier et al., 2010). These studies on host-range restriction of
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insect-specific flaviviruses and no-known-vector flaviviruses suggest that the latter have fewer host-
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range restriction barriers as the first step of the viral life cycle, entry/attachment, does not represent
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a barrier.
Influence of ecosystem modification on arboviruses. Primary ecosystems contain an exceptional
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diversity of animals and plants (Gibson et al., 2011; Myers et al., 2000). Nearly one-third of all known
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species are threatened with extinction due to ecosystems modification and habitat loss (IUCN, 2018). There is growing evidence that the loss of biodiversity alters pathogen transmission patterns (Keesing
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et al., 2010a, 2006a). Given the dramatic global environmental change and the unparalleled loss of biodiversity (Barnosky et al., 2011; Wake and Vredenburg, 2008), there is an urgent need to understand ecological mechanisms driving pathogen emergence.
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Hypotheses trying to explain the linkages between ecosystem modification and the upsurge in infectious diseases are coming from the fields of disease ecology and community ecology. There are currently three main hypotheses that are to some extent controversial (Figure 1A). The most widely accepted is the dilution effect hypothesis, which assumes that a high species diversity reduces the spread of pathogens by diluting the density of susceptible hosts for the pathogen of interest (Civitello et al., 2015; Cohen et al., 2016; Keesing et al., 2010a, 2006b; Pagán et al., 2012). Loss of biodiversity
can be advantageous for certain hosts (generalists) and amplifies their respective pathogens. In a nutshell, high biodiversity has a protective effect on infectious disease. Accordingly, the dilution effect aims at explaining differences in infection rates of (epidemic) pathogens that are able to infect humans and livestock. Numerous studies have shown that high biodiversity reduces pathogen transmission and infection rates in humans, wildlife, livestock, and plants (Begon et al., 2009; Civitello et al., 2015;
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Ezenwa et al., 2006; Keesing et al., 2010a; Khalil et al., 2016; Lacroix et al., 2013; Ostfeld and Keesing, 2012). The dilution effect hypothesis has so far only been studied for a single arbovirus, WNV. It was
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shown that a higher diversity of birds correlates with lower incidence of human infection in the United States (Allan et al., 2009; Swaddle and Calos, 2008). Another study found higher seroprevalence rates of WNV in birds in areas with a higher bird diversity (Levine et al., 2017). The study area was dominated
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by sub-optimal host species, which may explain the contrary observations. Other studies could also
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not confirm the dilution effect, suggesting that it is not generally applicable (Loss et al., 2009;
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Milholland et al., 2017; Ogden and Tsao, 2009; Wood et al., 2014). However, an increasingly
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widespread view suggests that neutral or contrary effects could occur under specific circumstances (Johnson and Thieltges, 2010; Keesing et al., 2010b, 2006a; Ostfeld and Keesing, 2012; Ostfeld and
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Keesing, 2000a; Ostfeld and Keesing, 2000b; Ostfeld and LoGiudice, 2003; Pongsiri et al., 2009; Schmidt
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and Ostfeld, 2001), but high biodiversity, especially in primary ecosystems, principally reduces pathogen prevalence rates (Cardinale et al., 2012).
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Whereas the dilution effect focuses on infection rates of a single pathogen in a single host, another hypothesis, the amplification effect hypothesis, takes into account that each host in a biodiverse ecosystem is infected with pathogens, thus causing a putative higher overall infection rate due to
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additive effects of pathogen carriage (Faust et al., 2017; Randolph and Dobson, 2012). Briefly, this hypothesis assumes that high host diversity translates into high diversity of pathogens (Randolph and Dobson, 2012). The idea of the amplification effect mainly arises from empirical studies and data from field experiments or natural populations is difficult to find. A third hypothesis, the intermediate disturbance hypothesis, predicts that local species diversity is maximized at intermediate intensity of disturbance (Molino and Sabatier, 2001). According to this
hypothesis, disturbance acts as a driver of diversity as it disrupts stable ecosystems and can induce movement of species from adjacent non-disturbed and highly disturbed ecosystems. However, studies have shown that the intermediate disturbance hypothesis is not broadly applicable to organisms and communities (Bongers et al., 2009; Fox, 2013). A recent study on the interplay between forest disturbance and mosquito species composition in Panama could not confirm the intermediate
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disturbance hypothesis as the highest diversity of mosquito species was found in old-growth forests (Loaiza et al., 2017). Notably, linkages between the intermediate disturbance hypothesis and infectious
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disease have not been explored yet.
The conflicting hypotheses and conflicting patterns of empirical data underline that more studies are needed to understand how biodiversity affects pathogen prevalence and infection risk. In particular,
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the effects of host-related factors, such as mobility, lifespan, and density, on prevalence patterns of
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specific pathogens need to be investigated. Studies in population ecology are generally performed
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within single host and single pathogen systems. However, to identify the underlying processes
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are of paramount importance.
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controlling infection risk, studies on multi-host and multi pathogen systems in natural communities
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4. Conclusions
Arboviruses are of the greatest importance for human and animal health worldwide. Multiple
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arboviruses have emerged in the recent past and caused epidemics of global concern. Knowledge of the mechanisms driving the emergence of viruses from their natural maintenance cycles to infect livestock and humans is still very limited. Enlightening studies are coming from the field of community
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ecology. However, studies have mainly focused on bacterial and parasitic pathogens and publications on viral infections are limited to single-host single-pathogen relationships. Studies of mosquito population compositions and patterns of viral infection in different ecosystems could help to identify critical factors fostering arbovirus emergence.
Acknowledgements
This work was funded by the Federal Ministry of Education and Research (BMBF) under project number 01KI1716 as part of the Research Network Zoonotic Infectious Diseases.
5. References Allan, B.F., Langerhans, R.B., Ryberg, W.A., Landesman, W.J., Griffin, N.W., Katz, R.S., Oberle, B.J.,
IP T
Schutzenhofer, M.R., Smyth, K.N., De St. Maurice, A., Clark, L., Crooks, K.R., Hernandez, D.E., McLean, R.G., Ostfeld, R.S., Chase, J.M., 2009. Ecological correlates of risk and incidence of
SC R
West Nile virus in the United States. Oecologia. https://doi.org/10.1007/s00442-008-1169-9
Anishchenko, M., Bowen, R.A., Paessler, S., Austgen, L., Greene, I.P., Weaver, S.C., 2006. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation. Proc. Natl.
U
Acad. Sci. 103, 4994–4999. https://doi.org/10.1073/pnas.0509961103
N
Apte-Deshpande, A.D., Paingankar, M.S., Gokhale, M.D., Deobagkar, D.N., 2014. Serratia odorifera
A
mediated enhancement in susceptibility of Aedes aegypti for chikungunya virus. Indian J. Med.
M
Res. 139, 762–768.
Barnosky, A.D., Matzke, N., Tomiya, S., Wogan, G.O.U., Swartz, B., Quental, T.B., Marshall, C.,
ED
McGuire, J.L., Lindsey, E.L., Maguire, K.C., Mersey, B., Ferrer, E.A., 2011. Has the Earth’s sixth
PT
mass extinction already arrived? Nature 471, 51–57. https://doi.org/10.1038/nature09678 Begon, M., Telfer, S., Burthe, S., Lambin, X., Smith, M.J., Paterson, S., 2009. Effects of abundance on
CC E
infection in natural populations: Field voles and cowpox virus. Epidemics 1, 35–46. https://doi.org/10.1016/j.epidem.2008.10.001
Bhatt, S., Gething, P., Brady, O., Messina, J., Farlow, A., Moyes, C., 2012. The global distribution and
A
burden of dengue. NIH-PA Author Manuscr. Nat. https://doi.org/10.1038/nature12060.The
Billecocq, A., Spiegel, M., Vialat, P., Kohl, A., Weber, F., Bouloy, M., Haller, O., 2004. NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription. J. Virol. 78, 9798–806. https://doi.org/10.1128/JVI.78.18.9798-9806.2004 Blair, C.D., 2011. Mosquito RNAi is the major innate immune pathway controlling arbovirus infection and transmission. Future Microbiol. 6, 265–277. https://doi.org/10.2217/fmb.11.11
Bongers, F., Poorter, L., Hawthorne, W.D., Sheil, D., 2009. The intermediate disturbance hypothesis applies to tropical forests, but disturbance contributes little to tree diversity. Ecol. Lett. https://doi.org/10.1111/j.1461-0248.2009.01329.x Bourtzis, K., Dobson, S.L., Xi, Z., Rasgon, J.L., Calvitti, M., Moreira, L. a., Bossin, H.C., Moretti, R., Baton, L.A., Hughes, G.L., Mavingui, P., Gilles, J.R.L., 2014. Harnessing mosquito-Wolbachia
IP T
symbiosis for vector and disease control. Acta Trop. 132, S150–S163. https://doi.org/10.1016/j.actatropica.2013.11.004
SC R
Brault, A.C., Powers, A.M., Holmes, E.C., Woelk, C.H., Weaver, S.C., 2002. Positively Charged Amino Acid Substitutions in the E2 Envelope Glycoprotein Are Associated with the Emergence of
https://doi.org/10.1128/JVI.76.4.1718-1730.2002
U
Venezuelan Equine Encephalitis Virus. J. Virol. 76, 1718–1730.
N
Brault, A.C., Powers, A.M., Weaver, S.C., 2002. Vector infection determinants of Venezuelan equine
A
encephalitis virus reside within the E2 envelope glycoprotein. J. Virol. 76, 6387–6392.
M
https://doi.org/10.1128/JVI.76.12.6387-6392.2002
Brown, J.E., Evans, B.R., Zheng, W., Obas, V., Barrera-Martinez, L., Egizi, A., Zhao, H., Caccone, A.,
ED
Powell, J.R., 2014. Human impacts have shaped historical and recent evolution in Aedes aegypti,
PT
the dengue and yellow fever mosquito. Evolution (N. Y). 68, 514–525. https://doi.org/10.1111/evo.12281
CC E
Bryant, J.E., Holmes, E.C., Barrett, A.D.T., 2007. Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas. PLoS Pathog. 3, e75. https://doi.org/10.1371/journal.ppat.0030075
A
Cardinale, B.J., Duffy, J.E., Gonzalez, A., Hooper, D.U., Perrings, C., Venail, P., Narwani, A., MacE, G.M., Tilman, D., Wardle, D.A., Kinzig, A.P., Daily, G.C., Loreau, M., Grace, J.B., Larigauderie, A., Srivastava, D.S., Naeem, S., 2012. Biodiversity loss and its impact on humanity. Nature. https://doi.org/10.1038/nature11148 Chancey, C., Grinev, A., Volkova, E., Rios, M., 2015. The global ecology and epidemiology of west nile virus. Biomed Res. Int. https://doi.org/10.1155/2015/376230
Charlier, N., Davidson, A., Dallmeier, K., Molenkamp, R., De Clercq, E., Neyts, J., 2010. Replication of not-known-vector flaviviruses in mosquito cells is restricted by intracellular host factors rather than by the viral envelope proteins. J. Gen. Virol. 91, 1693–1697. https://doi.org/10.1099/vir.0.019851-0 Chen, R., Puri, V., Fedorova, N., Lin, D., Hari, K.L., Jain, R., Rodas, J.D., Das, S.R., Shabman, R.S.,
the Global Expansion of Chikungunya Virus. J. Virol. 90, 10600–10611.
SC R
https://doi.org/10.1128/JVI.01166-16
IP T
Weaver, S.C., 2016. Comprehensive Genome Scale Phylogenetic Study Provides New Insights on
Civitello, D.J., Cohen, J., Fatima, H., Halstead, N.T., Liriano, J., McMahon, T.A., Ortega, C.N., Sauer,
dilution effect. Proc. Natl. Acad. Sci. 112, 8667–8671.
N
https://doi.org/10.1073/pnas.1506279112
U
E.L., Sehgal, T., Young, S., Rohr, J.R., 2015. Biodiversity inhibits parasites: Broad evidence for the
A
Coffey, L.L., Beeharry, Y., Borderia, a. V., Blanc, H., Vignuzzi, M., 2011. Arbovirus high fidelity variant
M
loses fitness in mosquitoes and mice. Proc. Natl. Acad. Sci. 108, 16038–16043. https://doi.org/10.1073/pnas.1111650108
ED
Coffey, L.L., Forrester, N., Tsetsarkin, K., Vasilakis, N., Weaver, S.C., 2013. Factors shaping the
PT
adaptive landscape for arboviruses: implications for the emergence of disease. Future Microbiol. 8, 155–176. https://doi.org/10.2217/fmb.12.139
CC E
Cohen, J.M., Civitello, D.J., Brace, A.J., Feichtinger, E.M., Ortega, C.N., Richardson, J.C., Sauer, E.L., Liu, X., Rohr, J.R., 2016. Spatial scale modulates the strength of ecological processes driving disease distributions. Proc. Natl. Acad. Sci. 113, E3359–E3364.
A
https://doi.org/10.1073/pnas.1521657113
Cook, S., Moureau, G., Kitchen, A., Gould, E.A., de Lamballerie, X., Holmes, E.C., Harbach, R.E., 2012. Molecular evolution of the insect-specific flaviviruses. J. Gen. Virol. 93, 223–234. https://doi.org/10.1099/vir.0.036525-0 Costa, E.A.P.D.A., Santos, E.M.D.M., Correia, J.C., Albuquerque, C.M.R. De, 2010. Impact of small variations in temperature and humidity on the reproductive activity and survival of Aedes
aegypti (Diptera, Culicidae). Rev. Bras. Entomol. https://doi.org/10.1590/S008556262010000300021 Dennison, N.J., Jupatanakul, N., Dimopoulos, G., 2014. The mosquito microbiota influences vector competence for human pathogens. Curr. Opin. Insect Sci. 3, 6–13. https://doi.org/10.1016/j.cois.2014.07.004
IP T
Descloux, E., Mangeas, M., Menkes, C.E., Lengaigne, M., Leroy, A., Tehei, T., Guillaumot, L., Teurlai, M., Gourinat, A.C., Benzler, J., Pfannstiel, A., Grangeon, J.P., Degallier, N., de Lamballerie, X.,
Trop. Dis. https://doi.org/10.1371/journal.pntd.0001470
SC R
2012. Climate-based models for understanding and forecasting dengue epidemics. PLoS Negl.
Dudas, G., Obbard, D.J., 2015. Are arthropods at the heart of virus evolution? Elife 2015, 1–3.
U
https://doi.org/10.7554/eLife.05378
N
Dutra, H.L.C., Rocha, M.N., Dias, F.B.S., Mansur, S.B., Caragata, E.P., Moreira, L.A., 2016. Wolbachia
A
Blocks Currently Circulating Zika Virus Isolates in Brazilian Aedes aegypti Mosquitoes. Cell Host
M
Microbe 19, 771–774. https://doi.org/10.1016/j.chom.2016.04.021 Elizondo-Quiroga, D., Elizondo-Quiroga, A., 2013. West Nile virus and its theories, a big puzzle in
ED
Mexico and Latin America. J. Glob. Infect. Dis. https://doi.org/10.4103/0974-777X.122014
PT
Elliott, R.M., 2014. Orthobunyaviruses: recent genetic and structural insights. Nat. Rev. Microbiol. 12, 673–685. https://doi.org/10.1038/nrmicro3332
CC E
Ezenwa, V.O., Godsey, M.S., King, R.J., Guptill, S.C., 2006. Avian diversity and West Nile virus: testing associations between biodiversity and infectious disease risk. Proc. Biol. Sci. https://doi.org/10.1098/rspb.2005.3284
A
Faust, C.L., Dobson, A.P., Gottdenker, N., Bloomfield, L.S.P., McCallum, H.I., Gillespie, T.R., DiukWasser, M., Plowright, R.K., 2017. Null expectations for disease dynamics in shrinking habitat: Dilution or amplification? Philos. Trans. R. Soc. B Biol. Sci. https://doi.org/10.1098/rstb.2016.0173 Focks, D.A., Brenner, R.J., Hayes, J., Daniels, E., 2000. Transmission thresholds for dengue in terms of Aedes aegypti pupae per person with discussion of their utility in source reduction efforts. Am.
J. Trop. Med. Hyg. https://doi.org/10.4269/ajtmh.2000.62.11 Forrester, N.L., Coffey, L.L., Weaver, S.C., 2014. Arboviral bottlenecks and challenges to maintaining diversity and fitness during mosquito transmission. Viruses. https://doi.org/10.3390/v6103991 Forrester, N.L., Guerbois, M., Seymour, R.L., Spratt, H., Weaver, S.C., 2012. Vector-Borne Transmission Imposes a Severe Bottleneck on an RNA Virus Population. PLoS Pathog. 8.
IP T
https://doi.org/10.1371/journal.ppat.1002897 Fortuna, C., Toma, L., Remoli, M.E., Amendola, A., Severini, F., Boccolini, D., Romi, R., Venturi, G.,
SC R
Rezza, G., Di Luca, M., 2018. Vector competence of Aedes albopictus for the Indian Ocean lineage (IOL) chikungunya viruses of the 2007 and 2017 outbreaks in Italy: a comparison
between strains with and without the E1:A226V mutation. Euro Surveill. Bull. Eur. sur les Mal.
U
Transm. = Eur. Commun. Dis. Bull. 23. https://doi.org/10.2807/1560-
N
7917.ES.2018.23.22.1800246
M
https://doi.org/10.1016/j.tree.2012.08.014
A
Fox, J.W., 2013. The intermediate disturbance hypothesis should be abandoned. Trends Ecol. Evol.
Franz, A.W.E., Kantor, A.M., Passarelli, A.L., Clem, R.J., 2015. Tissue barriers to arbovirus infection in
ED
mosquitoes. Viruses. https://doi.org/10.3390/v7072795
PT
Galiana-Arnoux, D., Dostert, C., Schneemann, A., Hoffmann, J.A., Imler, J.L., 2006. Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat. Immunol.
CC E
https://doi.org/10.1038/ni1335 Gibson, L., Lee, T.M., Koh, L.P., Brook, B.W., Gardner, T. a., Barlow, J., Peres, C. a., Bradshaw, C.J. a., Laurance, W.F., Lovejoy, T.E., Sodhi, N.S., 2011. Primary forests are irreplaceable for sustaining
A
tropical biodiversity. Nature 478, 378–381. https://doi.org/10.1038/nature10425
Gould, E. a, de Lamballerie, X., Zanotto, P.M.A., Holmes, E.C., 2003. Origins, evolution, and vector/host coadaptations within the genus Flavivirus. Adv. Virus Res. 59, 277–314. https://doi.org/10.1016/S0065-3527(03)59008-X Gould, E., Pettersson, J., Higgs, S., Charrel, R., de Lamballerie, X., 2017. Emerging arboviruses: Why today? One Heal. 4, 1–13. https://doi.org/10.1016/j.onehlt.2017.06.001
Greene, I.P., Paessler, S., Austgen, L., Anishchenko, M., Brault, A.C., Bowen, R.A., Weaver, S.C., 2005. Envelope Glycoprotein Mutations Mediate Equine Amplification and Virulence of Epizootic Venezuelan Equine Encephalitis Virus. J. Virol. 79, 9128–9133. https://doi.org/10.1128/JVI.79.14.9128-9133.2005 Grubaugh, N.D., Weger-Lucarelli, J., Murrieta, R.A., Fauver, J.R., Garcia-Luna, S.M., Prasad, A.N.,
IP T
Black, W.C., Ebel, G.D., 2016. Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching. Cell Host Microbe 19, 481–
SC R
492. https://doi.org/10.1016/j.chom.2016.03.002
Gubler, D.J., 2007. The Continuing Spread of West Nile Virus in the Western Hemisphere. Clin. Infect. Dis. 45, 1039–1046. https://doi.org/10.1086/521911
U
Guterres, A., de Oliveira, R.C., Fernandes, J., de Lemos, E.R.S., Schrago, C.G., 2017. New bunya-like
A
https://doi.org/10.1016/j.meegid.2017.01.019
N
viruses: Highlighting their relations. Infect. Genet. Evol. 49, 164–173.
M
Hendricks, D.A., Hardy, J.L., Reeves, W.C., 1983. Comparison of biological properties of St. Louis encephalitis and Rio bravo viruses. Am. J. Trop. Med. Hyg. 32, 602–609.
ED
Holmes, E.C., Twiddy, S.S., 2003. The origin, emergence and evolutionary genetics of dengue virus.
PT
Infect. Genet. Evol. https://doi.org/10.1016/S1567-1348(03)00004-2 Hopp, M.J., Foley, J.A., 2001. Global-scale relationships between climate and the dengue fever
CC E
vector, Aedes aegypti. Clim. Change. https://doi.org/10.1023/A:1010717502442 IUCN, 2018. The IUCN Red List of Threatened Species [WWW Document]. URL www.IUCNredlist.org (accessed 9.17.18).
A
Jia, Y., Moudy, R.M., Dupuis, A.P., Ngo, K.A., Maffei, J.G., Jerzak, G.V.S., Franke, M.A., Kauffman, E.B., Kramer, L.D., 2007. Characterization of a small plaque variant of West Nile virus isolated in New York in 2000. Virology. https://doi.org/10.1016/j.virol.2007.06.008 Johnson, P.T.J., Thieltges, D.W., 2010. Diversity, decoys and the dilution effect: how ecological communities affect disease risk. J. Exp. Biol. 213, 961–970. https://doi.org/10.1242/jeb.037721 Junglen, S., Korries, M., Grasse, W., Wieseler, J., Kopp, A., Hermanns, K., León-Juárez, M., Drosten, C.,
Kümmerer, B.M., 2017. Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle. mSphere 2, e00375-16. https://doi.org/10.1128/mSphere.0037516 Keesing, F., Belden, L.K., Daszak, P., Dobson, A., Harvell, C.D., Holt, R.D., Hudson, P., Jolles, A., Jones, K.E., Mitchell, C.E., Myers, S.S., Bogich, T., Ostfeld, R.S., 2010a. Impacts of biodiversity on the
IP T
emergence and transmission of infectious diseases. Nature 468, 647–652. https://doi.org/10.1038/nature09575
SC R
Keesing, F., Belden, L.K., Daszak, P., Dobson, A., Harvell, C.D., Holt, R.D., Hudson, P., Jolles, A., Jones, K.E., Mitchell, C.E., Myers, S.S., Bogich, T., Ostfeld, R.S., 2010b. Impacts of biodiversity on the emergence and transmission of infectious diseases. Nature.
U
https://doi.org/10.1038/nature09575
N
Keesing, F., Holt, R.D., Ostfeld, R.S., 2006a. Effects of species diversity on disease risk. Ecol. Lett.
A
https://doi.org/10.1111/j.1461-0248.2006.00885.x
M
Keesing, F., Holt, R.D., Ostfeld, R.S., 2006b. Effects of species diversity on disease risk. Ecol. Lett. 9, 485–498. https://doi.org/10.1111/j.1461-0248.2006.00885.x
ED
Khalil, H., Ecke, F., Evander, M., Magnusson, M., Hörnfeldt, B., 2016. Declining ecosystem health and
PT
the dilution effect. Sci. Rep. 6. https://doi.org/10.1038/srep31314 Kunkel, K.E., Novak, R.J., Lampman, R.L., Gu, W., 2006. Modeling the impact of variable climatic
CC E
factors on the crossover of Culex restauns and Culex pipiens (Diptera: Culicidae), vectors of West Nile virus in Illinois. Am. J. Trop. Med. Hyg. https://doi.org/74/1/168 [pii]
Lacroix, C., Jolles, A., Seabloom, E.W., Power, A.G., Mitchell, C.E., Borer, E.T., 2013. Non-random
A
biodiversity loss underlies predictable increases in viral disease prevalence. J. R. Soc. Interface 11, 20130947–20130947. https://doi.org/10.1098/rsif.2013.0947
Lafferty, K.D., Mordecai, E.A., 2016. The rise and fall of infectious disease in a warmer world. F1000Research. https://doi.org/10.12688/f1000research.8766.1 Lanciotti, R.S., Roehrig, J.T., Deubel, V., Smith, J., Parker, M., Steele, K., Crise, B., Volpe, K.E., Crabtree, M.B., Scherret, J.H., Hall, R.A., MacKenzie, J.S., Cropp, C.B., Panigrahy, B., Ostlund, E., Schmitt,
B., Malkinson, M., Banet, C., Weissman, J., Komar, N., Savage, H.M., Stone, W., McNamara, T., Gubler, D.J., 1999. Origin of the West Nile virus responsible for an outbreak of encephalitis in the Northeastern United States. Science (80-. ). 286, 2333–2337. https://doi.org/10.1126/science.286.5448.2333 Lauring, A.S., Andino, R., 2010. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog.
IP T
https://doi.org/10.1371/journal.ppat.1001005 Lawrie, C.H., Uzcátegui, N.Y., Armesto, M., Bell-Sakyi, L., Gould, E.A., 2004. Susceptibility of mosquito
SC R
and tick cell lines to infection with various flaviviruses. Med. Vet. Entomol. 18, 268–274. https://doi.org/10.1111/j.0269-283X.2004.00505.x
Levine, R.S., Hedeen, D.L., Hedeen, M.W., Hamer, G.L., Mead, D.G., Kitron, U.D., 2017. Avian species
N
https://doi.org/10.1186/s13071-017-1999-6
U
diversity and transmission of West Nile virus in Atlanta, Georgia. Parasit. Vectors.
A
Leyssen, P., Charlier, N., Lemey, P., Billoir, F., Vandamme, A.M., De Clercq, E., De Lamballerie, X.,
M
Neyts, J., 2002. Complete genome sequence, taxonomic assignment, and comparative analysis of the untranslated regions of the Modoc virus, a flavivirus with no known vector. Virology 293,
ED
125–140. https://doi.org/10.1006/viro.2001.1241
PT
Li, C.-X., Shi, M., Tian, J.-H., Lin, X.-D., Kang, Y.-J., Chen, L.-J., Qin, X.-C., Xu, J., Holmes, E.C., Zhang, Y.Z., 2015. Unprecedented genomic diversity of RNA viruses in arthropods reveals the ancestry of
CC E
negative-sense RNA viruses. Elife 4, 1–3. https://doi.org/10.7554/eLife.05378 Liu, Q., He, B., Huang, S.Y., Wei, F., Zhu, X.Q., 2014. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis. Lancet Infect. Dis. https://doi.org/10.1016/S1473-
A
3099(14)70718-2
Loaiza, J.R., Dutari, L.C., Rovira, J.R., Sanjur, O.I., Laporta, G.Z., Pecor, J., Foley, D.H., Eastwood, G., Kramer, L.D., Radtke, M., Pongsiri, M., 2017. Disturbance and mosquito diversity in the lowland tropical rainforest of central Panama. Sci. Rep. 7. https://doi.org/10.1038/s41598-017-07476-2 Loss, S.R., Hamer, G.L., Walker, E.D., Ruiz, M.O., Goldberg, T.L., Kitron, U.D., Brawn, J.D., 2009. Avian host community structure and prevalence of West Nile virus in Chicago, Illinois. Oecologia.
https://doi.org/10.1007/s00442-008-1224-6 Lucas, K.J., Myles, K.M., Raikhel, A.S., 2013. Small RNAs: A new frontier in mosquito biology. Trends Parasitol. https://doi.org/10.1016/j.pt.2013.04.003 Marklewitz, M., Handrick, S., Grasse, W., Kurth, A., Lukashev, A., Drosten, C., Ellerbrok, H., Leendertz, F.H., Pauli, G., Junglen, S., 2011. Gouleako Virus Isolated from West African Mosquitoes
IP T
Constitutes a Proposed Novel Genus in the Family Bunyaviridae. J. Virol. 85, 9227–9234. https://doi.org/10.1128/JVI.00230-11
SC R
Marklewitz, M., Zirkel, F., Kurth, A., Drosten, C., Junglen, S., 2015. Evolutionary and phenotypic
analysis of live virus isolates suggests arthropod origin of a pathogenic RNA virus family. Proc. Natl. Acad. Sci. 112, 7536–7541. https://doi.org/10.1073/pnas.1502036112
U
Marklewitz, M., Zirkel, F., Rwego, I.B., Heidemann, H., Trippner, P., Kurth, A., Kallies, R., Briese, T.,
N
Lipkin, W.I., Drosten, C., Gillespie, T.R., Junglen, S., 2013. Discovery of a Unique Novel Clade of
M
https://doi.org/10.1128/JVI.01862-13
A
Mosquito-Associated Bunyaviruses. J. Virol. 87, 12850–12865.
Milholland, M.T., Castro-Arellano, I., Arellano, E., Nava-García, E., Rangel-Altamirano, G., Gonzalez-
ED
Cozatl, F.X., Suzán, G., Schountz, T., González-Padrón, S., Vigueras, A., Rubio, A. V, Maikis, T.J.,
PT
Westrich, B.J., Martinez, J.A., Esteve-Gassent, M.D., Torres, M., Rodriguez-Ruiz, E.R., Hahn, D., Lacher, T.E., 2017. Species Identity Supersedes the Dilution Effect Concerning Hantavirus
CC E
Prevalence at Sites across Texas and México. ILAR J. 58, 401–412. https://doi.org/10.1093/ilar/ily001
Molino, J.-F., Sabatier, D., 2001. Tree Diversity in Tropical Rain Forests: A Validation of the
A
Intermediate Disturbance Hypothesis. Science (80-. ). 294, 1702–1704. https://doi.org/10.1126/science.1060284
Moureau, G., Cook, S., Lemey, P., Nougairede, A., Forrester, N.L., Khasnatinov, M., Charrel, R.N., Firth, A.E., Gould, E.A., De Lamballerie, X., 2015. New insights into flavivirus evolution, taxonomy and biogeographic history, extended by analysis of canonical and alternative coding sequences e0117849. PLoS One 10. https://doi.org/10.1371/journal.pone.0117849
Musso, D., Rodriguez-Morales, A.J., Levi, J.E., Cao-Lormeau, V.M., Gubler, D.J., 2018. Unexpected outbreaks of arbovirus infections: lessons learned from the Pacific and tropical America. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(18)30269-X Myers, N., Mittermeier, R.A., Mittermeier, C.G., da Fonseca, G.A.B., Kent, J., 2000. Biodiversity hotspots for conservation priorities. Nature 403, 853–858. https://doi.org/10.1038/35002501
homologous and heterologous interference. Virology 484, 51–58.
SC R
https://doi.org/10.1016/j.virol.2015.05.009
IP T
Nasar, F., Erasmus, J.H., Haddow, A.D., Tesh, R.B., Weaver, S.C., 2015. Eilat virus induces both
Nasar, F., Palacios, G., Gorchakov, R. V., Guzman, H., Da Rosa, A.P.T., Savji, N., Popov, V.L., Sherman, M.B., Lipkin, W.I., Tesh, R.B., Weaver, S.C., 2012. Eilat virus, a unique alphavirus with host range
U
restricted to insects by RNA replication. Proc. Natl. Acad. Sci. U. S. A. 109, 14622–7.
N
https://doi.org/10.1073/pnas.1204787109
A
Nowak, M.A., 1992. What is a quasispecies? Trends Ecol. Evol. 7, 118–121.
M
https://doi.org/10.1016/0169-5347(92)90145-2
Ogden, N.H., Tsao, J.I., 2009. Biodiversity and Lyme disease: Dilution or amplification? Epidemics.
ED
https://doi.org/10.1016/j.epidem.2009.06.002
PT
Ostfeld, R.S., Keesing, F., 2012. Effects of Host Diversity on Infectious Disease. Annu. Rev. Ecol. Evol. Syst. https://doi.org/10.1146/annurev-ecolsys-102710-145022
CC E
Ostfeld, R.S., Keesing, F., 2000. Biodiversity series: The function of biodiversity in the ecology of vector-borne zoonotic diseases. Can. J. Zool. https://doi.org/10.1139/z00-172
Ostfeld, R.S., Keesing, F., 2000. Biodiversity and disease risk: The case of Lyme disease. Conserv. Biol.
A
https://doi.org/10.1046/j.1523-1739.2000.99014.x
Ostfeld, R.S., LoGiudice, K., 2003. Community disassembly, biodiversity loss, and the erosion of an ecosystem service. Ecology 84, 1421–1427. https://doi.org/10.1890/02-3125 Pagán, I., González-Jara, P., Moreno-Letelier, A., Rodelo-Urrego, M., Fraile, A., Piñero, D., GarcíaArenal, F., 2012. Effect of biodiversity changes in disease risk: Exploring disease emergence in a plant-virus system. PLoS Pathog. 8, 47. https://doi.org/10.1371/journal.ppat.1002796
Paixão, E.S., Teixeira, M.G., Rodrigues, L.C., 2017. Zika, chikungunya and dengue: the causes and threats of new and re-emerging arboviral diseases. BMJ Glob. Heal. https://doi.org/10.1136/bmjgh-2017-000530 Palmer, W.H., Varghese, F.S., Van Rij, R.P., 2018. Natural variation in resistance to virus infection in dipteran insects. Viruses. https://doi.org/10.3390/v10030118
IP T
Patterson, E.I., Khanipov, K., Rojas, M.M., Kautz, T.F., Rockx-Brouwer, D., Golovko, G., Albayrak, L., Fofanov, Y., Forrester, N.L., 2018. Mosquito bottlenecks alter viral mutant swarm in a tissue and
SC R
time-dependent manner with contraction and expansion of variant positions and diversity. Virus Evol. 4. https://doi.org/10.1093/ve/vey001
Paz, S., 2015. Climate change impacts on West Nile virus transmission in a global context. Philos.
U
Trans. R. Soc. B Biol. Sci. https://doi.org/10.1098/rstb.2013.0561
N
Pongsiri, M.J., Roman, J., Ezenwa, V.O., Goldberg, T.L., Koren, H.S., Newbold, S.C., Ostfeld, R.S.,
A
Pattanayak, S.K., Salkeld, D.J., 2009. Biodiversity Loss Affects Global Disease Ecology.
M
Bioscience. https://doi.org/10.1525/bio.2009.59.11.6
Powell, J.R., Tabachnick, W.J., 2013. History of domestication and spread of Aedes aegypti--a review.
ED
Mem. Inst. Oswaldo Cruz. https://doi.org/10.1590/0074-0276130395
PT
Qu, B., Qi, X., Wu, X., Liang, M., Li, C., Cardona, C.J., Xu, W., Tang, F., Li, Z., Wu, B., Powell, K., Wegner, M., Li, D., Xing, Z., 2012. Suppression of the interferon and NF-κB responses by severe fever
CC E
with thrombocytopenia syndrome virus. J. Virol. 86, 8388–8401. https://doi.org/10.1128/JVI.00612-12
Randolph, S.E., Dobson, A.D.M., 2012. Pangloss revisited: A critique of the dilution effect and the
A
biodiversity-buffers-disease paradigm. Parasitology. https://doi.org/10.1017/S0031182012000200
Randolph, S.E., Rogers, D.J., 2010. The arrival, establishment and spread of exotic diseases: patterns and predictions. Nat. Rev. Microbiol. 8, 361–371. https://doi.org/10.1038/nrmicro2336 Reiter, P., 2001. Climate change and mosquito-borne disease. Environ. Health Perspect. https://doi.org/10.2307/3434853
Robinson, M.C., 1955. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features. Trans. R. Soc. Trop. Med. Hyg. 49, 28–32. Rohr, J.R., Dobson, A.P., Johnson, P.T.J., Kilpatrick, A.M., Paull, S.H., Raffel, T.R., Ruiz-Moreno, D., Thomas, M.B., 2011. Frontiers in climate change-disease research. Trends Ecol. Evol. 26, 270– 277. https://doi.org/10.1016/j.tree.2011.03.002
IP T
Roth, A., Mercier, A., Lepers, C., Hoy, D., Duituturaga, S., Benyon, E., Guillaumot, L., Souarès, Y., 2014. Concurrent outbreaks of dengue, chikungunya and zika virus infections – An unprecedented
https://doi.org/10.2807/1560-7917.ES2014.19.41.20929
SC R
epidemic wave of mosquito-borne viruses in the Pacific 2012–2014. Eurosurveillance 19.
Parasitol. https://doi.org/10.1016/j.pt.2017.12.004
U
Rückert, C., Ebel, G.D., 2018. How Do Virus–Mosquito Interactions Lead to Viral Emergence? Trends
N
Schmidt, K.A., Ostfeld, R.S., 2001. Biodiversity and the dilution effect in disease ecology. Ecology.
A
https://doi.org/10.1890/0012-9658(2001)082[0609:BATDEI]2.0.CO;2
M
Semenza, J.C., Menne, B., 2009. Climate change and infectious diseases in Europe. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(09)70104-5
ED
Shaman, J., Stieglitz, M., Stark, C., Le Blancq, S., Cane, M., 2002. Using a dynamic hydrology model to
PT
predict mosquito abundances in flood and swamp water. Emerg. Infect. Dis. https://doi.org/10.3201/eid0801.010049
CC E
Shi, M., Lin, X.D., Tian, J.H., Chen, L.J., Chen, X., Li, C.X., Qin, X.C., Li, J., Cao, J.P., Eden, J.S., Buchmann, J., Wang, W., Xu, J., Holmes, E.C., Zhang, Y.Z., 2016. Redefining the invertebrate RNA virosphere. Nature 540, 539–543. https://doi.org/10.1038/nature20167
A
Stapleford, K.A., Coffey, L.L., Lay, S., Bordería, A. V., Duong, V., Isakov, O., Rozen-Gagnon, K., AriasGoeta, C., Blanc, H., Beaucourt, S., Haliloǧlu, T., Schmitt, C., Bonne, I., Ben-Tal, N., Shomron, N., Failloux, A.B., Buchy, P., Vignuzzi, M., 2014. Emergence and transmission of arbovirus evolutionary intermediates with epidemic potential. Cell Host Microbe 15, 706–716. https://doi.org/10.1016/j.chom.2014.05.008 Swaddle, J.P., Calos, S.E., 2008. Increased avian diversity is associated with lower incidence of human
West Nile infection: Observation of the dilution effect. PLoS One 3. https://doi.org/10.1371/journal.pone.0002488 Tabachnick, W.J., 1991. Evolutionary Genetics and Arthropod-borne Disease: The Yellow Fever Mosquito. Am. Entomol. 37, 14–26. Tsetsarkin, K.A., Chen, R., Yun, R., Rossi, S.L., Plante, K.S., Guerbois, M., Forrester, N., Perng, G.C.,
IP T
Sreekumar, E., Leal, G., Huang, J., Mukhopadhyay, S., Weaver, S.C., 2014. Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes
SC R
albopictus mosquitoes. Nat. Commun. 5, 1–14. https://doi.org/10.1038/ncomms5084
Tsetsarkin, K.A., Vanlandingham, D.L., McGee, C.E., Higgs, S., 2007. A single mutation in Chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog.
U
https://doi.org/10.1371/journal.ppat.0030201
N
Turell, M.J., Dohm, D.J., Sardelis, M.R., O’Guinn, M.L., Andreadis, T.G., Blow, J.A., 2005. An update on
A
the potential of North American mosquitoes (Diptera: Culicidae) to transmit West Nile virus. J.
M
Med. Entomol. https://doi.org/10.1093/jmedent/42.1.57 Van Rij, R.P., Saleh, M.C., Berry, B., Foo, C., Houk, A., Antoniewski, C., Andino, R., 2006. The RNA
ED
silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila
PT
melanogaster. Genes Dev. https://doi.org/10.1101/gad.1482006 Vasilakis, N., Cardosa, J., Hanley, K.A., Holmes, E.C., Weaver, S.C., 2011. Fever from the forest:
CC E
Prospects for the continued emergence of sylvatic dengue virus and its impact on public health. Nat. Rev. Microbiol. https://doi.org/10.1038/nrmicro2595
Vazeille, M., Zouache, K., Vega-Rúa, A., Thiberge, J.M., Caro, V., Yébakima, A., Mousson, L.,
A
Piorkowski, G., Dauga, C., Vaney, M.C., Manni, M., Gasperi, G., De Lamballerie, X., Failloux, A.B., 2016. Importance of mosquito “quasispecies” in selecting an epidemic arthropod-borne virus. Sci. Rep. 6. https://doi.org/10.1038/srep29564
Vega-Rua, A., Zouache, K., Caro, V., Diancourt, L., Delaunay, P., Grandadam, M., Failloux, A.B., 2013. High Efficiency of Temperate Aedes albopictus to Transmit Chikungunya and Dengue Viruses in the Southeast of France. PLoS One. https://doi.org/10.1371/journal.pone.0059716
Wake, D.B., Vredenburg, V.T., 2008. Are we in the midst of the sixth mass extinction? A view from the world of amphibians. Proc. Natl. Acad. Sci. https://doi.org/10.1073/pnas.0801921105 Weaver, S.C., Ferro, C., Barrera, R., Boshell, J., Navarro, J.C., 2004. Venezuelan Equine Encephalitis. Annu. Rev. Entomol. 49, 141–174. https://doi.org/10.1146/annurev.ento.49.061802.123422 Weaver, S.C., Lecuit, M., 2015. Chikungunya Virus and the Global Spread of a Mosquito-Borne
IP T
Disease. N. Engl. J. Med. 372, 1231–1239. https://doi.org/10.1056/NEJMra1406035 Wernike, K., Conraths, F., Zanella, G., Granzow, H., Gache, K., Schirrmeier, H., Valas, S., Staubach, C.,
SC R
Marianneau, P., Kraatz, F., Höreth-Böntgen, D., Reimann, I., Zientara, S., Beer, M., 2014. Schmallenberg virus-Two years of experiences. Prev. Vet. Med. 116, 423–434. https://doi.org/10.1016/j.prevetmed.2014.03.021
U
Wood, C.L., Lafferty, K.D., DeLeo, G., Young, H.S., Hudson, P.J., Kuris, A.M., 2014. Does biodiversity
N
protect humans against infectious disease? Ecology. https://doi.org/10.1890/13-1041.1
A
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PT
M
ED
https://doi.org/10.3390/v8060174
A
Wuerth, J., Weber, F., 2016. Phleboviruses and the Type I Interferon Response. Viruses 8, 174.
Figure 1: Overview of factors contributing to arbovirus emergence. (A) Host abundance and pathogen diversity are illustrated according to different ecological hypothesis. The Dilution Effect Hypothesis (DEH) predicts a negative correlation between biodiversity and disease risk. The Amplification Effect Hypothesis (AEH) assumes a positive correlation between biodiversity and disease risk. The Intermediate Disturbance hypothesis (IDH) predicts the highest biodiversity in an intermediate
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disturbed ecosystem. (B) Arbovirus amplification cycles and spread. (C) Arbovirus dissemination and infection within a mosquito. The magnified area illustrates one of the bottlenecks in more detail
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including antiviral RNAi as an example for generating genetic diversity upon cell infection (modified
after Rückert and Ebel, 2018). Abbreviations are as follows: salivary glands (SG), basal lamina (BL), midgut epithelium (ME), midgut lumen (ML). Different mosquito and virus species are indicated by
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different colours. Genetically different virus variants are indicated by colour shading.
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