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Coat proteins, host factors and plant viral replication
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Coat proteins, host factors and plant viral replication Konstantin I Ivanov and Kristiina Ma¨kinen It was once believed that the sole biological function of viral coat protein (CP) is to encapsidate the viral genome, protecting it from degradation. The past several decades have witnessed a shift in this paradigm towards recognizing CPs as multifunctional proteins involved in almost every stage of the viral infection cycle. Such functional diversity is achieved via specific CP interactions with viral and host components in the infected cell. Different CP functions are tightly regulated both temporally and spatially through a variety of mechanisms including post-translational modifications and competing interactions. In the present review, we summarize the nonstructural functions of plant viral CPs, placing special emphasis on their roles in viral genome replication and translation. Address Department of Food and Environmental Sciences, P.O. Box 27, 00014 University of Helsinki, Finland Corresponding author: Ma¨kinen, Kristiina ([email protected])
Current Opinion in Virology 2012, 2:xx–yy This review comes from a themed issue on Virus replication in animals and plants Edited by Peter Nagy and Christopher Richardson
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Introduction Successful viral infection depends on the careful execution of several consecutive and often overlapping stages of the viral life cycle. Viral genome uncoating, translation, replication, suppression of host defenses, movement and encapsidation all must be tightly coordinated to ensure a productive infection. Such coordination can be achieved either by binding of certain combinations of regulatory proteins to cis-acting and trans-acting viral regulatory sequences or by spatial and/or temporal separation of different viral functions. Complex interactions between viral non-structural proteins and host factors also play important regulatory roles during viral infection [1]. Surprisingly enough, many non-structural functions have been attributed in recent decades to viral coat proteins (CPs), which were once thought to only encapsidate the viral genome, protecting it from degradation. Although virion assembly and dissociation remain the canonical CP functions, we now know that CPs represent truly multifunctional proteins involved in practically every stage of the www.sciencedirect.com
viral infection cycle. The CP functions include coordination of viral replication, translation and movement as well as modulation of host responses to viral infection and transmission of the virus to healthy plants. In the case of DNA viruses, CPs also facilitate nucleocytoplasmic shuttling of viral genomes. The non-structural functions of plant viral CPs are in the focus of this review.
Strategies to control CP expression in positive-sense RNA viruses Proper timing and proper amount of CP synthesis are essential for successful viral infection. Tight control over CP gene expression is required for temporal separation of early viral genome replication from late virion assembly and movement. In many positive-sense RNA (ssRNA(+)) viruses, such temporal control over CP expression is achieved by the late production of CP from subgenomic RNAs (sgRNAs; Figure 1a). sgRNAs are produced efficiently only when the replication cycle is already established, thus preventing premature particle assembly at the early stages of infection. This allows viral RNA replication to proceed in the absence of competing CP-mediated processes such as encapsidation or movement. Other ssRNA(+) viruses employ an alternative genome expression strategy based on the synthesis of a single polyprotein (Figure 1b), which is proteolytically processed to yield smaller individual proteins. In such viruses, CP and replication proteins are produced in equimolar ratio, making temporal control over CP more complicated and therefore far less understood. One possibility is that, in these viruses, CP turnover is regulated by targeted proteosomal degradation [2]. Another is that CP activity is regulated by post-translational modifications such as phosphorylation [3]. Yet another possibility is that virus-specific mechanisms boost viral RNA translation in the later stages of infection [4], bringing about large amount of CP required for virion assembly. Despite the different strategies used by different viruses to control CP production and availability, such control is universally required for CPs to properly perform their various functions.
Coordination of replication cycle in ssRNA(+) viruses Infection with Brome mosaic virus (BMV; genera Bromovirus) offers a good example of how different amounts of CP present at different time points regulate the progression of viral infection cycle (reviewed in [5]). BMV CP is expressed from subgenomic RNA4 that is transcribed from the negative-strand of genomic RNA3 (Figure 1a). Early in viral infection, when the amount of CP is limited, CP enhances replication through binding to an RNA element named SLC within the 30 -tRNA-like Current Opinion in Virology 2012, 2:1–7
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Figure 1
(a) Virion Assembly
BMV [CP]↑
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CP-mediated down-regulation of 1a and 2a translation and VRC assembly late in infection
Enhancement of (-)-strand RNA synthesis early in infection
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(b) Cell-to-cell Movement
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Virus-specific translational pathway enhancing CP production[4]
PVA
Phosphorylationmediated regulation of CP functions[3]
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structure that contains the core promoter for genomic minus-strand RNA synthesis [6]. As CP levels rise towards the later stages of infection, the role of CP changes from one of replication enhancer to its inhibitor. Furthermore, at higher concentrations, CP also inhibits viral RNA translation [7,8]. Such functional switching is achieved through concentration-dependent binding of CP to a second RNA element called B box located in the 50 UTR of BMV RNA1 and RNA2 [7]. Thus, the carefully orchestrated changes in CP levels regulate the progression of BMV infection cycle from genome replication/translation to virion assembly. Interestingly, BMV virion assembly requires ongoing replication to increase CP specificity for packaging viral RNAs [9]. Another well-studied example of a virus requiring CP for efficient viral RNA translation/replication is Alfalfa mosaic virus (AMV; genus Alfamovirus). In a phenomenon termed ‘genome activation’, AMV genomic RNAs require the presence of a few ‘activating’ CP molecules for infectivity. One explanation of this phenomenon is that AMV CP enhances viral RNA translation through simultaneous binding to secondary structures at the 30 ends of AMV RNAs and 50 -cap-bound translation initiation factors, thus forming a closed-loop RNA structure [10,11,12,13]. In this manner, AMV CP may enhance viral RNA translation by mimicking the function of the poly(A) binding protein (PABP) in translation of cellular mRNAs. In an alternative model, interaction with AMV CP allows the 30 -UTR of viral RNA to assume a highly ordered tRNA-like conformation [14]. This conformation is then recognized by viral RNA-dependent RNA polymerase (RdRP) as an initiation site for minus-strand RNA synthesis. The formation of the RdRP-RNA complex is significantly enhanced in the presence of CP [12], suggesting that CP plays an active role during initiation of viral replication. Because both models are supported by independent experimental evidence, they may not be mutually exclusive. That is, AMV CP may enhance both viral RNA translation and replication, depending on the stage of infection. To determine whether this is indeed the case, new
experimental approaches will be needed to separately assess the AMV CP involvement in viral translation and replication in vivo in the context of AMV infection.
Assembly of viral replication complexes Many RNA viruses assemble their viral replication complexes (VRCs) on intracellular membranes. This process is associated with rearrangement of, for example, endoplasmic reticulum (ER) and formation of membrane vesicles, which represent organelle-like compartments for viral replication [15,16]. These vesicles contain viral replication proteins and RNA templates shielded from host defenses and sequestered from competing processes. A new and surprising twist to this concept is that BMV CP itself has the intrinsic property to induce ER membrane rearrangements and formation of vesicles similar to those present in infected cells [17]. Thus, CP may play an important and previously unsuspected role in organizing local membrane environment for efficient viral replication. Furthermore, BMV CP co-localizes with sites of viral replication in infected cells, suggesting that replication and virion assembly are spatially coupled. Such coupling is beneficial for the virus because it allows selective encapsidation of newly synthesized viral RNA and its protection from nuclease degradation immediately after synthesis. In some viruses, CP is dispensable for replication. For example, replication of Tobacco mosaic virus (TMV; genus Tobamovirus) does not require CP, but its expression leads to a more rapid appearance of VRCs and increase in their size [18]. Therefore, TMV CP may play an accessory role in the formation of VRCs, possibly through regulation of sgRNA production.
Chaperone-mediated regulation of CP functions during replication Infection with many plant viruses induces the expression of host HSP70 genes, encoding molecular chaperones [19]. In potyviruses, members of the heat shock protein 70 family interact with viral RdRP and appear to be putative VRC components [2,20]. Moreover, a CPmediated defect in the replication of Potato virus A
Figure 1 Legend Schematic representation of the CP functions of Brome mosaic virus (BMV) and Potato virus A (PVA). (a) The tripartite BMV genome consisting of three (+)-sense ssRNAs is shown in blue (RNA1), green (RNA2) and red (RNA3). BMV CP is translated from the subgenomic RNA4 (sgRNA4), which is synthesized from the ()-strand of genomic RNA3. Early in BMV infection, when the amount of CP is limited, CP enhances genomic ()-strand RNA synthesis through recognition of the 30 -terminal RNA element SLC containing a binding motif for the viral replicase. As CP levels rise towards the later stages of infection, CP binding to the second RNA element, B box, leads to inhibition of viral replication complex (VRC) assembly and downregulation of replicase protein translation. Finally, at high CP levels, viral RNAs are encapsidated and transported to the next cell via plasmodesmata, presumably in the form of capsids moving along virus-induced tubular structures. Downregulated viral proteins are shown as dotted boxes. Rising CP levels in late stages of infection are indicated in bold face; low CP levels early in infection are shown in smaller font size. (b) The (+)sense ssRNA genome of PVA encodes a single polyprotein, which is proteolytically processed to yield ten individual proteins. Because CP and other PVA proteins are produced in equimolar ratio, control over CP synthesis and availability is achieved by different mechanisms than in BMV. The first putative mechanism is the chaperone-mediated regulation of CP turnover. Early in viral infection, excess of CP is removed by means of HSP70/CPIPmediated proteosomal degradation, allowing viral RNA replication to efficiently proceed in the absence of premature particle assembly. Late in infection, rising CP levels overpower the HSP70/CPIP-mediated degradation machinery, leading to cessation of viral translation/replication and promoting virion assembly and movement to the next cell via plasmodesmata. The second putative mechanism is the regulation of CP activities, such as virion assembly, by phosphorylation. The third putative mechanism involves virus-specific boosting of viral RNA translation late in infection, bringing about large amount of CP required for virion assembly. www.sciencedirect.com
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(PVA; genus Potyvirus) is observed in HSP70-silenced plants [2]. J-domain proteins CPIPs, co-chaperones of HSP70, interact with potyviral CPs and represent important susceptibility factors for potyvirus infection [2,21]. Interestingly, ectopic expression of PVA CP inhibits viral gene expression, but CPIP is able to counteract the inhibition in association with HSP70 [2]. Thus, the HSP70/ CPIP-dependent mechanism may prevent premature particle assembly at the early stages of infection, allowing for efficient viral RNA replication and translation. Another J-domain protein, designated NbDnaJ, binds to the CP of Potato virus X (PVX; genus Potexvirus) in Nicotiana benthamiana [22]. The protein specifically recognizes a structure in the 50 untranslated region of PVX RNA called stem-loop 1 (SL1), which interacts with CP and is essential for viral replication and movement [23]. Experiments in NbDnaJ-silenced plants or in plants overexpressing NbDnaJ suggest that NbDnaJ is a negative regulator of PVX replication and movement at the early stages of infection, acting through interaction with CP and SL1 RNA [22]. An emerging picture is that Jdomain co-chaperones are often associated with plant viral replication, but they do not necessarily exert their effects through CPs. For example, a J-domian protein of yeast, Ydj1p, is involved in the formation of BMV VRCs and ()-strand synthesis, but it functions through viral replication proteins [24].
Caulimovirus). CPs of MSV, TYLCV and CaMV all contain nuclear localization signals (NLSs) and are imported into the nucleus [28–31]. Furthermore, TYLCV CP and CaMV CP interact with the NLS receptor importin a, a central component of the canonical nuclear import pathway [31,32]. In addition to NLS, TYLCV CP also contains a functional nuclear export signal (NES) [33], required for export from the nucleus and, consequently, for nucleocytoplasmic shuttling. A similar role in viral nuclear transport has been proposed for nucleocapsid (N) proteins of ssRNA() nucleorhabdoviruses, which, like geminiviruses and caulimoviruses, also replicate in the cell nucleus. N proteins of nucleorhabdoviruses Sonchus yellow net virus (SYNV), Maize fine streak virus (MFSV) and Potato yellow dwarf virus (PYDV) contain functional NLS sequences, mediating their nuclear import [34–36]. The N protein of PYDV has been shown to interact with the NLS receptor importin a, confirming its role in nuclear import [37]. Rather unexpectedly, functional nuclear and nucleolar localization signals have been recently identified in CPs of at least two plant ssRNA(+) viruses replicating in the cell cytoplasm [38,39]. Although the roles of CPs in nuclear trafficking of plant DNA viruses and ssRNA() nucleorhabdoviruses are fairly well understood, the mechanisms underlying CP nuclear import in viruses replicating in the cytoplasm remain to be elucidated.
Viral movement and vector transmission Coordination of replication cycle in ssRNA(S) and dsRNA viruses CP also plays an important role in the replication of ssRNA() and dsRNA viruses. Tight association of the nucleocapsid protein (N-protein) of Tomato Spotted Wild Virus (TSWV; genus Tospovirus) with both TSWV RNAs and RdRp is required for the formation of transcriptionally active RNP-complexes [25]. In addition, the Nprotein of TSWV can enhance translation of the ambisense S RNA in the presence of a silencing suppressor NSs [26]. The molecular details of replication of plant dsRNA reoviruses remain to be studied, but they probably share the same replication mechanisms as animal reoviruses. Replication of animal reoviruses, for example rotaviruses, closely follows the steps involved in the assembly of an icosahedral capsid [27].
To establish a successful infection, a virus has to move from cell-to-cell and over long distances in the infected plant, and then has to be transported to new healthy plants by small mobile organisms, known as viral vectors. CP is required for cell-to-cell spread of many viruses, either in the form of virions or in a non-encapsidated form through a variety of mechanisms including transport through plasmodesmata-penetrating tubules and CP interactions with viral movement proteins (MPs). Furthermore, nearly all plant viruses recruit CP for systemic leaf-to-leaf movement via plant vasculature. CP is also essential for plant-to-plant transmission of many viruses by arthropods, nematodes and fungal zoospores. These CP functions have been reviewed in depth by several authors [40–42,43,44] and therefore are not discussed here in detail.
Nucleocytoplasmic shuttling of viral genomes
Plant response to viral infection
In contrast to RNA viruses replicating in the cytoplasm, plant DNA viruses have to enter the nucleus for replication and then exit the nucleus for cell-to-cell movement. Many DNA viruses require CPs for such nucleocytoplasmic shuttling of their genomes. Most of our knowledge of CP involvement in this process comes from studies of two monopartite geminiviruses Maize streak virus (MSV; genus Mastervirus) and Tomato yellow leaf curl virus (TYCLV; genus Begomovirus), as well as the plant dsDNA pararetrovirus Cauliflower mosaic virus (CaMV; genus
Plant resistance genes (R-genes) confer resistance to various viruses [45]. In many cases, viral CPs represent pathogen molecules specifically recognized by the R-gene products. For example, specific recognition of PVX CP by a protein encoded by the Rx1 resistance gene of Solanum tumberosum leads to resistance against PVX [46]. In a similar manner, the products of HRT and RCY1 genes of Arabidopsis thaliana confer CP-mediated resistance to Turnip crinkle virus (TCV; genus Carmovirus) [47] and Cucumber mosaic virus (CMV; genus Cucumovirus) [48], respectively.
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RNA interference (RNAi), also known as gene silencing, represents another important plant defense mechanism. To overcome host-mediated RNAi and to sustain vigorous replication, plant viruses typically encode proteins called gene silencing suppressors. CPs of several viruses, such as TCV and Citrus tristeza virus (CTV; genus Closterovirus), can function as gene silencing suppressors [49–51].
Post-translational modifications Post-translational modifications, such as phosphorylation, are used by some plant viruses to regulate their CP functions. Phosphorylation of PVX CP by plant cytoplasmic protein kinases(s) induces conformational changes in the protein, converting the non-translatable encapsidated PVX RNA into a form translatable in vitro [52]. Phosphorylation of CaMV CP precursor at several sites by the host protein kinase CK2 has a role in symptom development and viral infectivity [53,54]. Phosphorylation of PVA CP by host protein kinase(s) inhibits its binding to RNA in vitro, suggesting that a CP phosphorylation-mediated mechanism exists to control the amount of CP available for interaction with viral RNA (Figure 1b) [3]. CK2 is one of the kinases phosphorylating PVA CP and mutation of a major CK2 phosphorylation site in CP leads to loss of viral infectivity, with the virus being restricted to single infected cells [55]. CP of Plum pox virus (PPV; genus Potyvirus) is modified with O-linked b-N-acetylglucosamine (O-GlcNAc) at several sites by an O-GlcNAc transferase named SECRET AGENT (SEC) [56–59]. Although the high conservation of the glycosylation sites is evident among different PPV isolates, the exact role of this modification in viral infection remains to be determined. PVA CP ubiquitination and subsequent degradation are enhanced by CPIP over expression [2], providing an example for how plant HSP70/CPIP complex can regulate CP accumulation early in viral infection (Figure 1b). Interestingly, protein kinase CK2 may be involved in the regulation of CP turnover (Lo˜hmus, Hafre´n and Ma¨kinen, unpublished), linking the CK2mediated CP phosphorylation with the ubiquitination and degradation pathway. Further studies are necessary to determine whether the ubiquitin-mediated degradation is indeed the mechanism for controlling the amount of potyviral CP at the early stages of infection. If this is the case, the amount of newly produced CP would gradually increase towards the later stages of infection and eventually overpower the HSP70/CPIP machinery, leading to cessation of translation and replication, thereby promoting virion assembly.
Interaction with host proteins There is growing evidence that plant viral CPs are involved in a variety of interactions with host proteins, which modify the cellular environment to selectively www.sciencedirect.com
benefit viral infection. The outer capsid protein P2 of Rice dwarf virus (RDV; genus Phytoreovirus) interacts with ent-kaurene oxidases, leading to reduced biosynthesis of plant growth hormones gibberilins in infected plants [60]. This contributes to plant growth stunting and associated rice dwarf symptoms. In addition, the interaction between P2 and ent-kaurene oxidases may reduce phytoalexin biosynthesis, thus compromising host defenses against viral replication [60]. There are other examples of CP interactions with host proteins that affect the course of viral infection. Interaction of Tomato mosaic virus (ToMV; genus Tobamovirus) CP with a novel plant factor IP-L affects viral long distance movement [61]. Binding of ER-associated protein NbPCIP1 to PVX CP promotes viral replication [62]. Downregulation of another PVX CP binding partner, plastocyanin, decreases virus accumulation in chloroplasts and reduces symptom severity in whole plants [63]. Finally, BMV CP binding to oxidoreductase HCP1 controls BMV infection in barley [64]. The interplay between CP and host proteins in the regulation of viral replication and/or translation is an emerging and promising area of research. Such regulation may be achieved, for example, through competition between CP and host proteins for the same regulatory elements in viral RNA. In line with this possibility, interaction of host pseudouridine synthase 4 (Pus4) with the CP-binding element SLC in the 30 -tRNA-like structure inhibits BMV RNA accumulation [65].
Conclusions Taken together, the results summarized above show that plant viral CPs, in addition to protecting viral genomes, have many important non-structural functions including regulation of genome replication and translation. Future studies will further advance our understanding of the molecular mechanisms underlying these functions and will almost certainly reveal novel interactions of CPs with viral and host components. The advent of a new generation of experimental approaches, such as high-throughput proteomics, has provided a unique opportunity to simultaneously identify multiple CP-interacting partners. This information can be used to better characterize specific complexes formed by CPs at different stages of viral infection, thus providing more mechanistic insight into the various CP functions. This, in turn, may lead to the development of new antiviral strategies against existing and emerging plant viral diseases.
Acknowledgements We sincerely apologize to colleagues whose publications could not be cited here owing to space constraints. We thank Drs. Anders Hafre´n and Olga Samuilova for critical reading of the manuscript. The support of the Academy of Finland to K.M. is gratefully acknowledged (grant 1138329).
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: Current Opinion in Virology 2012, 2:1–7
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6 Virus replication in animals and plants
of special interest of outstanding interest
1.
Nagy PD, Pogany J: Global genomics and proteomics approaches to identify host factors as targets to induce resistance against Tomato bushy stunt virus. Advances in Virus Research 2010, 76:123-177.
2.
Hafren A, Hofius D, Ronnholm G, Sonnewald U, Makinen K: HSP70 and its cochaperone CPIP promote potyvirus infection in Nicotiana benthamiana by regulating viral coat protein functions. Plant Cell 2010, 22:523-535. Evidence for the role of two host chaperones, HSP70 and CPIP, in the functional regulation of PVA CP. CPIP-mediated delivery of PVA CP to HSP70 promotes CP ubiquitination and degradation. 3.
Ivanov KI, Puustinen P, Merits A, Saarma M, Ma¨kinen K: Phosphorylation down-regulates the RNA binding function of the coat protein of potato virus A. Journal of Biological Chemistry 2001, 276:13530-13540.
4.
Eskelin K, Hafren A, Rantalainen KI, Makinen K: Potyviral VPg enhances viral RNA translation and inhibits reporter mRNA translation in planta. Journal of Virology 2011, 85:9210-9221.
5.
Kao CC, Ni P, Hema M, Huang X, Dragnea B: The coat protein leads the way: an update on basic and applied studies with the brome mosaic virus coat protein. Molecular Plant Pathology 2011, 12:403-412.
6.
Chapman MR, Kao CC: A minimal RNA promoter for minusstrand RNA synthesis by the brome mosaic virus polymerase complex. Journal of Molecular Biology 1999, 286:709-720.
7.
Yi G, Letteney E, Kim CH, Kao CC: Brome mosaic virus capsid protein regulates accumulation of viral replication proteins by binding to the replicase assembly RNA element. RNA 2009, 15:615-626. The authors demonstrate that binding of BMV CP to the B box structure in viral RNAs 1 and 2 inhibits the accumulation of viral replication proteins in a CP concentration-dependent manner. In addition, B box serves as an enhancer element for replicase assembly
15. den Boon JA, Ahlquist P: Organelle-like membrane compartmentalization of positive-strand RNA virus replication factories. Annual Review of Microbiology 2010, 64:241-256. 16. Verchot J: Wrapping membranes around plant virus infection. Current Opinion in Virology 2011, 1:388-395. 17. Bamunusinghe D, Seo JK, Rao ALN: Subcellular localization and rearrangement of endoplasmic reticulum by brome mosaic virus capsid protein. Journal of Virology 2011, 85:2953-2963. Evidence for the spatial and functional overlap between BMV CP and viral replication. BMV CP itself has the intrinsic property to induce the formation of ER-derived vesicles. 18. Asurmendi S, Berg RH, Koo JC, Beachy RN: Coat protein regulates formation of replication complexes during tobacco mosaic virus infection. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:1415-1420. The authors show that despite the fact that TMV CP is not absolutely required for virus replication, it regulates the formation of VRCs and enhances movement protein accumulation. 19. Nagy PD, Wang RY, Pogany J, Hafren A, Makinen K: Emerging picture of host chaperone and cyclophilin roles in RNA virus replication. Virology 2011, 411:374-382. 20. Dufresne PJ, Thivierge K, Cotton S, Beauchemin C, Ide C, Ubalijoro E, Laliberte JF, Fortin MG: Heat shock 70 protein interaction with Turnip mosaic virus RNA-dependent RNA polymerase within virus-induced membrane vesicles. Virology 2008, 374:217-227. 21. Hofius D, Maier AT, Dietrich C, Jungkunz I, Bornke F, Maiss E, Sonnewald U: Capsid protein-mediated recruitment of host DnaJ-like proteins is required for Potato virus Y infection in tobacco plants. Journal of Virology 2007, 81:11870-11880. The authors demonstrate that J-domain proteins, CPIPs, interact with PVY CP and represent important susceptibility factors for PVY infection. Expression of dominant-negative mutants of CPIPs confers resistance to PVY.
8.
Yi G, Vaughan RC, Yarbrough I, Dharmaiah S, Kao CC: RNA binding by the brome mosaic virus capsid protein and the regulation of viral RNA accumulation. Journal of Molecular Biology 2009, 391:314-326.
22. Cho SY, Cho WK, Sohn SH, Kim KH: Interaction of the host protein NbDnaJ with Potato virus X minus-strand stem-loop 1 RNA and capsid protein affects viral replication and movement. Biochemical and Biophysical Research Communications 2012, 417:451-456. Evidence for the interaction between a J-domain protein from Nicotiana benthamiana, NbDnaJ, PVX CP and a PVX RNA element essential for viral replication and movement. PVX replication and movement are inhibited by excess NbDnaJ and accelerated in its absence.
9.
Annamalai P, Rao ALN: Packaging of brome mosaic virus subgenomic RNA is functionally coupled to replicationdependent transcription and translation of coat protein. Journal of Virology 2006, 80:10096-10108.
23. Lough TJ, Lee RH, Emerson SJ, Forster RL, Lucas WJ: Functional analysis of the 50 untranslated region of potexvirus RNA reveals a role in viral replication and cell-to-cell movement. Virology 2006, 351:455-465.
10. Neeleman L, Olsthoorn RC, Linthorst HJ, Bol JF: Translation of a nonpolyadenylated viral RNA is enhanced by binding of viral coat protein or polyadenylation of the RNA. Proceedings of the National Academy of Sciences of the United States of America 2001, 98:14286-14291. The authors show that binding of AMV CP to the 30 UTR of viral RNAs can mimic binding of the poly(A) binding protein (PABP) to the 30 poly(A) tail of cellular mRNAs. 11. Neeleman L, Linthorst HJM, Bol JF: Efficient translation of alfamovirus RNAs requires the binding of coat protein dimers to the 30 termini of the viral RNAs. Journal of General Virology 2004, 85:231-240. 12. Reichert VL, Choi M, Petrillo JE, Gehrke L: Alfalfa mosaic virus coat protein bridges RNA and RNA-dependent RNA polymerase in vitro. Virology 2007, 364:214-226. The authors show that AMV and TSV CPs enhance binding of replicase proteins to a structural element in the 30 -UTR of viral RNA. 13. Bol JF: Replication of alfamo- and ilarviruses: role of the coat protein. Annual Review of Phytopathology 2005, 43:39-62. A detailed review of the replication strategies of alfamoviruses and ilarviruses, with special emphasis on the role of CP. 14. Guogas LM, Filman DJ, Hogle JM, Gehrke L: Cofolding organizes alfalfa mosaic virus RNA and coat protein for replication. Science 2004, 306:2108-2111. Crystal structure of the AMV CP peptide-viral RNA complex reveals that, in the presence of CP, RNA assumes a highly ordered conformation essential for viral replication. Current Opinion in Virology 2012, 2:1–7
24. Tomita Y, Mizuno T, Dı´ez J, Naito S, Ahlquist P, Ishikawa M: Mutation of host DnaJ homolog inhibits brome mosaic virus negative-strand RNA synthesis. Journal of Virology 2003, 77:2990-2997. 25. Kormelink R: The molecular biology of tospoviruses and resistance strategies. In The Bunyaviridae: Molecular and Cellular Biology. Edited by Plyusnin A, Elliott RM. Horizon Scientific Press; 2011. 26. Geerts-Dimitriadou C, Lu YY, Geertsema C, Goldbach R, Kormelink R: Analysis of the Tomato spotted wilt virus ambisense S RNA-encoded hairpin structure in translation. PLoS ONE 2012, 7:e31013. 27. Trask SD, McDonald SM, Patton JT: Structural insights into the coupling of virion assembly and rotavirus replication. Nature Reviews Microbiology 2012, 10:165-177. 28. Liu H, Boulton MI, Thomas CL, Prior DA, Oparka KJ, Davies JW: Maize streak virus coat protein is karyophyllic and facilitates nuclear transport of viral DNA. Molecular Plant-Microbe Interactions 1999, 12:894-900. 29. Kunik T, Palanichelvam K, Czosnek H, Citovsky V, Gafni Y: Nuclear import of the capsid protein of tomato yellow leaf curl virus (TYLCV) in plant and insect cells. Plant Journal 1998, 13:393-399. 30. Leclerc D, Chapdelaine Y, Hohn T: Nuclear targeting of the Cauliflower mosaic virus coat protein. Journal of Virology 1999, 73:553-560. www.sciencedirect.com
Please cite this article in press as: Ivanov KI, Ma¨kinen K. Coat proteins, host factors and plant viral replication, Curr Opin Virol (2012), http://dx.doi.org/10.1016/j.coviro.2012.10.001
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Coat proteins, host factors and plant viral replication Ivanov and Ma¨kinen 7
31. Karsies A, Merkle T, Szurek B, Bonas U, Hohn T, Leclerc D: Regulated nuclear targeting of Cauliflower mosaic virus. Journal of General Virology 2002, 83:1783-1790. 32. Krichevsky A, Kozlovsky SV, Gafni Y, Citovsky V: Nuclear import and export of plant virus proteins and genomes. Molecular Plant Pathology 2006, 7:131-146. A comprehensive review of the mechanisms of plant viral nuclear import and export.
early initiation step. Journal of Virology 2003, 77:511-522. 51. Lu R, Folimonov A, Shintaku M, Li WX, Falk BW, Dawson WO, Ding SW: Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:15742-15747.
33. Rhee Y, Gurel F, Gafni Y, Dingwall C, Citovsky V: A genetic system for detection of protein nuclear import and export. Nature Biotechnology 2000, 18:433-437.
52. Atabekov JG, Rodionova NP, Karpova OV, Kozlovsky SV, Novikov VK, Arkhipenko MV: Translational activation of encapsidated Potato virus X RNA by coat protein phosphorylation. Virology 2001, 286:466-474.
34. Goodin MM, Austin J, Tobias R, Fujita M, Morales C, Jackson AO: Interactions and nuclear import of the N and P proteins of sonchus yellow net virus, a plant nucleorhabdovirus. Journal of Virology 2001, 75:9393-9406.
53. Chapdelaine Y, Kirk D, Karsies A, Hohn T, Leclerc D: Mutation of capsid protein phosphorylation sites abolishes Cauliflower mosaic virus infectivity. Journal of Virology 2002, 76:1174811752.
35. Tsai CW, Redinbaugh MG, Willie KJ, Reed S, Goodin M, Hogenhout SA: Complete genome sequence and in planta subcellular localization of maize fine streak virus proteins. Journal of Virology 2005, 79:5304-5314.
54. Champagne J, Laliberte-Gagne ME, Leclerc D: Phosphorylation of the termini of Cauliflower mosaic virus precapsid protein is important for productive infection. Molecular Plant-Microbe Interactions 2007, 20:648-658.
36. Martin K, Kopperud K, Chakrabarty R, Banerjee R, Brooks R, Goodin MM: Transient expression in Nicotiana benthamiana fluorescent marker lines provides enhanced definition of protein localization, movement and interactions in planta. Plant Journal 2009, 59:150-162.
55. Ivanov KI, Puustinen P, Gabrenaite R, Vihinen H, Ro¨nnstrand L, Valmu L, Kalkkinen N, Ma¨kinen K: Phosphorylation of the potyvirus capsid protein by protein kinase CK2 and its relevance for virus infection. Plant Cell 2003, 15:2124-2139. The authors show that PVA CP is phosphorylated by the protein kinase CK2 and that mutation of a major CK2 phosphorylation site in CP renders PVA noninfectious.
37. Anderson G, Wang R, Bandyopadhyay A, Goodin M: The nucleocapsid protein of potato yellow dwarf virus: protein interactions and nuclear import mediated by a non-canonical nuclear localization signal. Frontiers in Plant Science 2012, 3:14. 38. Haupt S, Stroganova T, Ryabov E, Kim SH, Fraser G, Duncan G, Mayo MA, Barker H, Taliansky M: Nucleolar localization of potato leafroll virus capsid proteins. Journal of General Virology 2005, 86:2891-2896. 39. Olspert A, Paves H, Toomela R, Tamm T, Truve E: Cocksfoot mottle sobemovirus coat protein contains two nuclear localization signals. Virus Genes 2010, 40:423-431. 40. Scholthof HB: Plant virus transport: motions of functional equivalence. Trends in Plant Science 2005, 10:376-382. 41. Niehl A, Heinlein M: Cellular pathways for viral transport through plasmodesmata. Protoplasma 2011, 248:75-99. 42. Campbell RN: Fungal transmission of plant viruses. Annual Review of Phytopathology 1996, 34:87-108. 43. Callaway A, Giesman-Cookmeyer D, Gillock ET, Sit TL, Lommel SA: The multifunctional capsid proteins of plant RNA viruses. Annual Review of Phytopathology 2001, 39:419-460. An in-depth review of the multiple functions of plant viral CPs. 44. Bol JF: Role of capsid proteins. Methods in Molecular Biology 2008, 451:21-31. 45. Soosaar JL, Burch-Smith TM, Dinesh-Kumar SP: Mechanisms of plant resistance to viruses. Nature Reviews Microbiology 2005, 3:789-798. 46. Bendahmane A, Kanyuka K, Baulcombe DC: The Rx gene from potato controls separate virus resistance and cell death responses. Plant Cell 1999, 11:781-792. 47. Cooley MB, Pathirana S, WuF H.J., Kachroo P, Klessig DF: Members of the Arabidopsis HRT/RPP8 family of resistance genes confer resistance to both viral and oomycete pathogens. Plant Cell 2000, 12:663-676. 48. Sekine KT, Ishihara T, Hase S, Kusano T, Shah J, Takahashi H: Single amino acid alterations in Arabidopsis thaliana RCY1 compromise resistance to Cucumber mosaic virus, but differentially suppress hypersensitive response-like cell death. Plant Molecular Biology 2006, 62:669-682. 49. Thomas CL, Leh V, Lederer C, Maule AJ: Turnip crinkle virus coat protein mediates suppression of RNA silencing in Nicotiana benthamiana. Virology 2003, 306:33-41. 50. Qu F, Ren T, Morris TJ: The coat protein of turnip crinkle virus suppresses posttranscriptional gene silencing at an
www.sciencedirect.com
56. Rosario Ferna´ndez-Ferna´ndez M, Camafeita E, Bonay P, Meacute E, Albar JP, Garcı´a JA: The capsid protein of a plant single-stranded RNA virus is modified by O-linked N-acetylglucosamine. Journal of Biological Chemistry 2002, 277:135-140. 57. Chen D, Juarez S, Hartweck L, Alamillo JM, Simon-Mateo C, Perez JJ, Fernandez-Fernandez MR, Olszewski NE, Garcia JA: Identification of secret agent as the O-GlcNAc transferase that participates in Plum pox virus infection. Journal of Virology 2005, 79:9381-9387. 58. Scott CL, Hartweck LM, de Jesu´s Pe´rez J, Chen D, Garcı´a JA, Olszewski NE: SECRET AGENT, an Arabidopsis thaliana OGlcNAc transferase, modifies the Plum pox virus capsid protein. FEBS Letters 2006, 580:5829-5835. 59. Kim Y-, Udeshi ND, Balsbaugh JL, Shabanowitz J, Hunt DF, Olszewski NE: O-GlcNAcylation of the Plum pox virus capsid protein catalyzed by SECRET AGENT: characterization of OGlcNAc sites by electron transfer dissociation mass spectrometry. Amino Acids 2011, 40:869-876. 60. Zhu S, Gao F, Cao X, Chen M, Ye G, Wei C, Li Y: The rice dwarf virus P2 protein interacts with ent-kaurene oxidases in vivo, leading to reduced biosynthesis of gibberellins and rice dwarf symptoms. Plant Physiology 2005, 139:1935-1945. 61. Li Y, Wu MY, Song HH, Hu X, Qiu BS: Identification of a tobacco protein interacting with tomato mosaic virus coat protein and facilitating long-distance movement of virus. Archives of Virology 2005, 150:1993-2008. 62. Park MR, Park SH, Cho SY, Kim KH: Nicotiana benthamiana protein, NbPCIP1, interacting with Potato virus X coat protein plays a role as susceptible factor for viral infection. Virology 2009, 386:257-269. 63. Qiao Y, Li HF, Wong SM, Fan ZF: Plastocyanin transit peptide interacts with Potato virus X coat protein, while silencing of plastocyanin reduces coat protein accumulation in chloroplasts and symptom severity in host plants. Molecular Plant-Microbe Interactions 2009, 22:1523-1534. 64. Okinaka Y, Mise K, Okuno T, Furusawa I: Characterization of a novel barley protein, HCP1, that interacts with the Brome mosaic virus coat protein. Molecular Plant-Microbe Interactions 2003, 16:352-359. 65. Zhu J, Gopinath K, Murali A, Yi G, Hayward SD, Zhu H, Kao C: RNA-binding proteins that inhibit RNA virus infection. Proceedings of the National Academy of Sciences of the United States of America 2007, 104:3129-3134.
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Coat proteins, host factors and plant viral replication Konstantin I Ivanov and Kristiina Ma¨kinen It was once believed that the sole biological function of viral coat protein (CP) is to encapsidate the viral genome, protecting it from degradation. The past several decades have witnessed a shift in this paradigm towards recognizing CPs as multifunctional proteins involved in almost every stage of the viral infection cycle. Such functional diversity is achieved via specific CP interactions with viral and host components in the infected cell. Different CP functions are tightly regulated both temporally and spatially through a variety of mechanisms including post-translational modifications and competing interactions. In the present review, we summarize the nonstructural functions of plant viral CPs, placing special emphasis on their roles in viral genome replication and translation. Address Department of Food and Environmental Sciences, P.O. Box 27, 00014 University of Helsinki, Finland Corresponding author: Ma¨kinen, Kristiina ([email protected])
Current Opinion in Virology 2012, 2:xx–yy This review comes from a themed issue on Virus replication in animals and plants Edited by Peter Nagy and Christopher Richardson
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Introduction Successful viral infection depends on the careful execution of several consecutive and often overlapping stages of the viral life cycle. Viral genome uncoating, translation, replication, suppression of host defenses, movement and encapsidation all must be tightly coordinated to ensure a productive infection. Such coordination can be achieved either by binding of certain combinations of regulatory proteins to cis-acting and trans-acting viral regulatory sequences or by spatial and/or temporal separation of different viral functions. Complex interactions between viral non-structural proteins and host factors also play important regulatory roles during viral infection [1]. Surprisingly enough, many non-structural functions have been attributed in recent decades to viral coat proteins (CPs), which were once thought to only encapsidate the viral genome, protecting it from degradation. Although virion assembly and dissociation remain the canonical CP functions, we now know that CPs represent truly multifunctional proteins involved in practically every stage of the www.sciencedirect.com
viral infection cycle. The CP functions include coordination of viral replication, translation and movement as well as modulation of host responses to viral infection and transmission of the virus to healthy plants. In the case of DNA viruses, CPs also facilitate nucleocytoplasmic shuttling of viral genomes. The non-structural functions of plant viral CPs are in the focus of this review.
Strategies to control CP expression in positive-sense RNA viruses Proper timing and proper amount of CP synthesis are essential for successful viral infection. Tight control over CP gene expression is required for temporal separation of early viral genome replication from late virion assembly and movement. In many positive-sense RNA (ssRNA(+)) viruses, such temporal control over CP expression is achieved by the late production of CP from subgenomic RNAs (sgRNAs; Figure 1a). sgRNAs are produced efficiently only when the replication cycle is already established, thus preventing premature particle assembly at the early stages of infection. This allows viral RNA replication to proceed in the absence of competing CP-mediated processes such as encapsidation or movement. Other ssRNA(+) viruses employ an alternative genome expression strategy based on the synthesis of a single polyprotein (Figure 1b), which is proteolytically processed to yield smaller individual proteins. In such viruses, CP and replication proteins are produced in equimolar ratio, making temporal control over CP more complicated and therefore far less understood. One possibility is that, in these viruses, CP turnover is regulated by targeted proteosomal degradation [2]. Another is that CP activity is regulated by post-translational modifications such as phosphorylation [3]. Yet another possibility is that virus-specific mechanisms boost viral RNA translation in the later stages of infection [4], bringing about large amount of CP required for virion assembly. Despite the different strategies used by different viruses to control CP production and availability, such control is universally required for CPs to properly perform their various functions.
Coordination of replication cycle in ssRNA(+) viruses Infection with Brome mosaic virus (BMV; genera Bromovirus) offers a good example of how different amounts of CP present at different time points regulate the progression of viral infection cycle (reviewed in [5]). BMV CP is expressed from subgenomic RNA4 that is transcribed from the negative-strand of genomic RNA3 (Figure 1a). Early in viral infection, when the amount of CP is limited, CP enhances replication through binding to an RNA element named SLC within the 30 -tRNA-like Current Opinion in Virology 2012, 2:1–7
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Figure 1
(a) Virion Assembly
BMV [CP]↑
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CP-mediated down-regulation of 1a and 2a translation and VRC assembly late in infection
Enhancement of (-)-strand RNA synthesis early in infection
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Virus-specific translational pathway enhancing CP production[4]
PVA
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structure that contains the core promoter for genomic minus-strand RNA synthesis [6]. As CP levels rise towards the later stages of infection, the role of CP changes from one of replication enhancer to its inhibitor. Furthermore, at higher concentrations, CP also inhibits viral RNA translation [7,8]. Such functional switching is achieved through concentration-dependent binding of CP to a second RNA element called B box located in the 50 UTR of BMV RNA1 and RNA2 [7]. Thus, the carefully orchestrated changes in CP levels regulate the progression of BMV infection cycle from genome replication/translation to virion assembly. Interestingly, BMV virion assembly requires ongoing replication to increase CP specificity for packaging viral RNAs [9]. Another well-studied example of a virus requiring CP for efficient viral RNA translation/replication is Alfalfa mosaic virus (AMV; genus Alfamovirus). In a phenomenon termed ‘genome activation’, AMV genomic RNAs require the presence of a few ‘activating’ CP molecules for infectivity. One explanation of this phenomenon is that AMV CP enhances viral RNA translation through simultaneous binding to secondary structures at the 30 ends of AMV RNAs and 50 -cap-bound translation initiation factors, thus forming a closed-loop RNA structure [10,11,12,13]. In this manner, AMV CP may enhance viral RNA translation by mimicking the function of the poly(A) binding protein (PABP) in translation of cellular mRNAs. In an alternative model, interaction with AMV CP allows the 30 -UTR of viral RNA to assume a highly ordered tRNA-like conformation [14]. This conformation is then recognized by viral RNA-dependent RNA polymerase (RdRP) as an initiation site for minus-strand RNA synthesis. The formation of the RdRP-RNA complex is significantly enhanced in the presence of CP [12], suggesting that CP plays an active role during initiation of viral replication. Because both models are supported by independent experimental evidence, they may not be mutually exclusive. That is, AMV CP may enhance both viral RNA translation and replication, depending on the stage of infection. To determine whether this is indeed the case, new
experimental approaches will be needed to separately assess the AMV CP involvement in viral translation and replication in vivo in the context of AMV infection.
Assembly of viral replication complexes Many RNA viruses assemble their viral replication complexes (VRCs) on intracellular membranes. This process is associated with rearrangement of, for example, endoplasmic reticulum (ER) and formation of membrane vesicles, which represent organelle-like compartments for viral replication [15,16]. These vesicles contain viral replication proteins and RNA templates shielded from host defenses and sequestered from competing processes. A new and surprising twist to this concept is that BMV CP itself has the intrinsic property to induce ER membrane rearrangements and formation of vesicles similar to those present in infected cells [17]. Thus, CP may play an important and previously unsuspected role in organizing local membrane environment for efficient viral replication. Furthermore, BMV CP co-localizes with sites of viral replication in infected cells, suggesting that replication and virion assembly are spatially coupled. Such coupling is beneficial for the virus because it allows selective encapsidation of newly synthesized viral RNA and its protection from nuclease degradation immediately after synthesis. In some viruses, CP is dispensable for replication. For example, replication of Tobacco mosaic virus (TMV; genus Tobamovirus) does not require CP, but its expression leads to a more rapid appearance of VRCs and increase in their size [18]. Therefore, TMV CP may play an accessory role in the formation of VRCs, possibly through regulation of sgRNA production.
Chaperone-mediated regulation of CP functions during replication Infection with many plant viruses induces the expression of host HSP70 genes, encoding molecular chaperones [19]. In potyviruses, members of the heat shock protein 70 family interact with viral RdRP and appear to be putative VRC components [2,20]. Moreover, a CPmediated defect in the replication of Potato virus A
Figure 1 Legend Schematic representation of the CP functions of Brome mosaic virus (BMV) and Potato virus A (PVA). (a) The tripartite BMV genome consisting of three (+)-sense ssRNAs is shown in blue (RNA1), green (RNA2) and red (RNA3). BMV CP is translated from the subgenomic RNA4 (sgRNA4), which is synthesized from the ()-strand of genomic RNA3. Early in BMV infection, when the amount of CP is limited, CP enhances genomic ()-strand RNA synthesis through recognition of the 30 -terminal RNA element SLC containing a binding motif for the viral replicase. As CP levels rise towards the later stages of infection, CP binding to the second RNA element, B box, leads to inhibition of viral replication complex (VRC) assembly and downregulation of replicase protein translation. Finally, at high CP levels, viral RNAs are encapsidated and transported to the next cell via plasmodesmata, presumably in the form of capsids moving along virus-induced tubular structures. Downregulated viral proteins are shown as dotted boxes. Rising CP levels in late stages of infection are indicated in bold face; low CP levels early in infection are shown in smaller font size. (b) The (+)sense ssRNA genome of PVA encodes a single polyprotein, which is proteolytically processed to yield ten individual proteins. Because CP and other PVA proteins are produced in equimolar ratio, control over CP synthesis and availability is achieved by different mechanisms than in BMV. The first putative mechanism is the chaperone-mediated regulation of CP turnover. Early in viral infection, excess of CP is removed by means of HSP70/CPIPmediated proteosomal degradation, allowing viral RNA replication to efficiently proceed in the absence of premature particle assembly. Late in infection, rising CP levels overpower the HSP70/CPIP-mediated degradation machinery, leading to cessation of viral translation/replication and promoting virion assembly and movement to the next cell via plasmodesmata. The second putative mechanism is the regulation of CP activities, such as virion assembly, by phosphorylation. The third putative mechanism involves virus-specific boosting of viral RNA translation late in infection, bringing about large amount of CP required for virion assembly. www.sciencedirect.com
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(PVA; genus Potyvirus) is observed in HSP70-silenced plants [2]. J-domain proteins CPIPs, co-chaperones of HSP70, interact with potyviral CPs and represent important susceptibility factors for potyvirus infection [2,21]. Interestingly, ectopic expression of PVA CP inhibits viral gene expression, but CPIP is able to counteract the inhibition in association with HSP70 [2]. Thus, the HSP70/ CPIP-dependent mechanism may prevent premature particle assembly at the early stages of infection, allowing for efficient viral RNA replication and translation. Another J-domain protein, designated NbDnaJ, binds to the CP of Potato virus X (PVX; genus Potexvirus) in Nicotiana benthamiana [22]. The protein specifically recognizes a structure in the 50 untranslated region of PVX RNA called stem-loop 1 (SL1), which interacts with CP and is essential for viral replication and movement [23]. Experiments in NbDnaJ-silenced plants or in plants overexpressing NbDnaJ suggest that NbDnaJ is a negative regulator of PVX replication and movement at the early stages of infection, acting through interaction with CP and SL1 RNA [22]. An emerging picture is that Jdomain co-chaperones are often associated with plant viral replication, but they do not necessarily exert their effects through CPs. For example, a J-domian protein of yeast, Ydj1p, is involved in the formation of BMV VRCs and ()-strand synthesis, but it functions through viral replication proteins [24].
Caulimovirus). CPs of MSV, TYLCV and CaMV all contain nuclear localization signals (NLSs) and are imported into the nucleus [28–31]. Furthermore, TYLCV CP and CaMV CP interact with the NLS receptor importin a, a central component of the canonical nuclear import pathway [31,32]. In addition to NLS, TYLCV CP also contains a functional nuclear export signal (NES) [33], required for export from the nucleus and, consequently, for nucleocytoplasmic shuttling. A similar role in viral nuclear transport has been proposed for nucleocapsid (N) proteins of ssRNA() nucleorhabdoviruses, which, like geminiviruses and caulimoviruses, also replicate in the cell nucleus. N proteins of nucleorhabdoviruses Sonchus yellow net virus (SYNV), Maize fine streak virus (MFSV) and Potato yellow dwarf virus (PYDV) contain functional NLS sequences, mediating their nuclear import [34–36]. The N protein of PYDV has been shown to interact with the NLS receptor importin a, confirming its role in nuclear import [37]. Rather unexpectedly, functional nuclear and nucleolar localization signals have been recently identified in CPs of at least two plant ssRNA(+) viruses replicating in the cell cytoplasm [38,39]. Although the roles of CPs in nuclear trafficking of plant DNA viruses and ssRNA() nucleorhabdoviruses are fairly well understood, the mechanisms underlying CP nuclear import in viruses replicating in the cytoplasm remain to be elucidated.
Viral movement and vector transmission Coordination of replication cycle in ssRNA(S) and dsRNA viruses CP also plays an important role in the replication of ssRNA() and dsRNA viruses. Tight association of the nucleocapsid protein (N-protein) of Tomato Spotted Wild Virus (TSWV; genus Tospovirus) with both TSWV RNAs and RdRp is required for the formation of transcriptionally active RNP-complexes [25]. In addition, the Nprotein of TSWV can enhance translation of the ambisense S RNA in the presence of a silencing suppressor NSs [26]. The molecular details of replication of plant dsRNA reoviruses remain to be studied, but they probably share the same replication mechanisms as animal reoviruses. Replication of animal reoviruses, for example rotaviruses, closely follows the steps involved in the assembly of an icosahedral capsid [27].
To establish a successful infection, a virus has to move from cell-to-cell and over long distances in the infected plant, and then has to be transported to new healthy plants by small mobile organisms, known as viral vectors. CP is required for cell-to-cell spread of many viruses, either in the form of virions or in a non-encapsidated form through a variety of mechanisms including transport through plasmodesmata-penetrating tubules and CP interactions with viral movement proteins (MPs). Furthermore, nearly all plant viruses recruit CP for systemic leaf-to-leaf movement via plant vasculature. CP is also essential for plant-to-plant transmission of many viruses by arthropods, nematodes and fungal zoospores. These CP functions have been reviewed in depth by several authors [40–42,43,44] and therefore are not discussed here in detail.
Nucleocytoplasmic shuttling of viral genomes
Plant response to viral infection
In contrast to RNA viruses replicating in the cytoplasm, plant DNA viruses have to enter the nucleus for replication and then exit the nucleus for cell-to-cell movement. Many DNA viruses require CPs for such nucleocytoplasmic shuttling of their genomes. Most of our knowledge of CP involvement in this process comes from studies of two monopartite geminiviruses Maize streak virus (MSV; genus Mastervirus) and Tomato yellow leaf curl virus (TYCLV; genus Begomovirus), as well as the plant dsDNA pararetrovirus Cauliflower mosaic virus (CaMV; genus
Plant resistance genes (R-genes) confer resistance to various viruses [45]. In many cases, viral CPs represent pathogen molecules specifically recognized by the R-gene products. For example, specific recognition of PVX CP by a protein encoded by the Rx1 resistance gene of Solanum tumberosum leads to resistance against PVX [46]. In a similar manner, the products of HRT and RCY1 genes of Arabidopsis thaliana confer CP-mediated resistance to Turnip crinkle virus (TCV; genus Carmovirus) [47] and Cucumber mosaic virus (CMV; genus Cucumovirus) [48], respectively.
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RNA interference (RNAi), also known as gene silencing, represents another important plant defense mechanism. To overcome host-mediated RNAi and to sustain vigorous replication, plant viruses typically encode proteins called gene silencing suppressors. CPs of several viruses, such as TCV and Citrus tristeza virus (CTV; genus Closterovirus), can function as gene silencing suppressors [49–51].
Post-translational modifications Post-translational modifications, such as phosphorylation, are used by some plant viruses to regulate their CP functions. Phosphorylation of PVX CP by plant cytoplasmic protein kinases(s) induces conformational changes in the protein, converting the non-translatable encapsidated PVX RNA into a form translatable in vitro [52]. Phosphorylation of CaMV CP precursor at several sites by the host protein kinase CK2 has a role in symptom development and viral infectivity [53,54]. Phosphorylation of PVA CP by host protein kinase(s) inhibits its binding to RNA in vitro, suggesting that a CP phosphorylation-mediated mechanism exists to control the amount of CP available for interaction with viral RNA (Figure 1b) [3]. CK2 is one of the kinases phosphorylating PVA CP and mutation of a major CK2 phosphorylation site in CP leads to loss of viral infectivity, with the virus being restricted to single infected cells [55]. CP of Plum pox virus (PPV; genus Potyvirus) is modified with O-linked b-N-acetylglucosamine (O-GlcNAc) at several sites by an O-GlcNAc transferase named SECRET AGENT (SEC) [56–59]. Although the high conservation of the glycosylation sites is evident among different PPV isolates, the exact role of this modification in viral infection remains to be determined. PVA CP ubiquitination and subsequent degradation are enhanced by CPIP over expression [2], providing an example for how plant HSP70/CPIP complex can regulate CP accumulation early in viral infection (Figure 1b). Interestingly, protein kinase CK2 may be involved in the regulation of CP turnover (Lo˜hmus, Hafre´n and Ma¨kinen, unpublished), linking the CK2mediated CP phosphorylation with the ubiquitination and degradation pathway. Further studies are necessary to determine whether the ubiquitin-mediated degradation is indeed the mechanism for controlling the amount of potyviral CP at the early stages of infection. If this is the case, the amount of newly produced CP would gradually increase towards the later stages of infection and eventually overpower the HSP70/CPIP machinery, leading to cessation of translation and replication, thereby promoting virion assembly.
Interaction with host proteins There is growing evidence that plant viral CPs are involved in a variety of interactions with host proteins, which modify the cellular environment to selectively www.sciencedirect.com
benefit viral infection. The outer capsid protein P2 of Rice dwarf virus (RDV; genus Phytoreovirus) interacts with ent-kaurene oxidases, leading to reduced biosynthesis of plant growth hormones gibberilins in infected plants [60]. This contributes to plant growth stunting and associated rice dwarf symptoms. In addition, the interaction between P2 and ent-kaurene oxidases may reduce phytoalexin biosynthesis, thus compromising host defenses against viral replication [60]. There are other examples of CP interactions with host proteins that affect the course of viral infection. Interaction of Tomato mosaic virus (ToMV; genus Tobamovirus) CP with a novel plant factor IP-L affects viral long distance movement [61]. Binding of ER-associated protein NbPCIP1 to PVX CP promotes viral replication [62]. Downregulation of another PVX CP binding partner, plastocyanin, decreases virus accumulation in chloroplasts and reduces symptom severity in whole plants [63]. Finally, BMV CP binding to oxidoreductase HCP1 controls BMV infection in barley [64]. The interplay between CP and host proteins in the regulation of viral replication and/or translation is an emerging and promising area of research. Such regulation may be achieved, for example, through competition between CP and host proteins for the same regulatory elements in viral RNA. In line with this possibility, interaction of host pseudouridine synthase 4 (Pus4) with the CP-binding element SLC in the 30 -tRNA-like structure inhibits BMV RNA accumulation [65].
Conclusions Taken together, the results summarized above show that plant viral CPs, in addition to protecting viral genomes, have many important non-structural functions including regulation of genome replication and translation. Future studies will further advance our understanding of the molecular mechanisms underlying these functions and will almost certainly reveal novel interactions of CPs with viral and host components. The advent of a new generation of experimental approaches, such as high-throughput proteomics, has provided a unique opportunity to simultaneously identify multiple CP-interacting partners. This information can be used to better characterize specific complexes formed by CPs at different stages of viral infection, thus providing more mechanistic insight into the various CP functions. This, in turn, may lead to the development of new antiviral strategies against existing and emerging plant viral diseases.
Acknowledgements We sincerely apologize to colleagues whose publications could not be cited here owing to space constraints. We thank Drs. Anders Hafre´n and Olga Samuilova for critical reading of the manuscript. The support of the Academy of Finland to K.M. is gratefully acknowledged (grant 1138329).
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: Current Opinion in Virology 2012, 2:1–7
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of special interest of outstanding interest
1.
Nagy PD, Pogany J: Global genomics and proteomics approaches to identify host factors as targets to induce resistance against Tomato bushy stunt virus. Advances in Virus Research 2010, 76:123-177.
2.
Hafren A, Hofius D, Ronnholm G, Sonnewald U, Makinen K: HSP70 and its cochaperone CPIP promote potyvirus infection in Nicotiana benthamiana by regulating viral coat protein functions. Plant Cell 2010, 22:523-535. Evidence for the role of two host chaperones, HSP70 and CPIP, in the functional regulation of PVA CP. CPIP-mediated delivery of PVA CP to HSP70 promotes CP ubiquitination and degradation. 3.
Ivanov KI, Puustinen P, Merits A, Saarma M, Ma¨kinen K: Phosphorylation down-regulates the RNA binding function of the coat protein of potato virus A. Journal of Biological Chemistry 2001, 276:13530-13540.
4.
Eskelin K, Hafren A, Rantalainen KI, Makinen K: Potyviral VPg enhances viral RNA translation and inhibits reporter mRNA translation in planta. Journal of Virology 2011, 85:9210-9221.
5.
Kao CC, Ni P, Hema M, Huang X, Dragnea B: The coat protein leads the way: an update on basic and applied studies with the brome mosaic virus coat protein. Molecular Plant Pathology 2011, 12:403-412.
6.
Chapman MR, Kao CC: A minimal RNA promoter for minusstrand RNA synthesis by the brome mosaic virus polymerase complex. Journal of Molecular Biology 1999, 286:709-720.
7.
Yi G, Letteney E, Kim CH, Kao CC: Brome mosaic virus capsid protein regulates accumulation of viral replication proteins by binding to the replicase assembly RNA element. RNA 2009, 15:615-626. The authors demonstrate that binding of BMV CP to the B box structure in viral RNAs 1 and 2 inhibits the accumulation of viral replication proteins in a CP concentration-dependent manner. In addition, B box serves as an enhancer element for replicase assembly
15. den Boon JA, Ahlquist P: Organelle-like membrane compartmentalization of positive-strand RNA virus replication factories. Annual Review of Microbiology 2010, 64:241-256. 16. Verchot J: Wrapping membranes around plant virus infection. Current Opinion in Virology 2011, 1:388-395. 17. Bamunusinghe D, Seo JK, Rao ALN: Subcellular localization and rearrangement of endoplasmic reticulum by brome mosaic virus capsid protein. Journal of Virology 2011, 85:2953-2963. Evidence for the spatial and functional overlap between BMV CP and viral replication. BMV CP itself has the intrinsic property to induce the formation of ER-derived vesicles. 18. Asurmendi S, Berg RH, Koo JC, Beachy RN: Coat protein regulates formation of replication complexes during tobacco mosaic virus infection. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:1415-1420. The authors show that despite the fact that TMV CP is not absolutely required for virus replication, it regulates the formation of VRCs and enhances movement protein accumulation. 19. Nagy PD, Wang RY, Pogany J, Hafren A, Makinen K: Emerging picture of host chaperone and cyclophilin roles in RNA virus replication. Virology 2011, 411:374-382. 20. Dufresne PJ, Thivierge K, Cotton S, Beauchemin C, Ide C, Ubalijoro E, Laliberte JF, Fortin MG: Heat shock 70 protein interaction with Turnip mosaic virus RNA-dependent RNA polymerase within virus-induced membrane vesicles. Virology 2008, 374:217-227. 21. Hofius D, Maier AT, Dietrich C, Jungkunz I, Bornke F, Maiss E, Sonnewald U: Capsid protein-mediated recruitment of host DnaJ-like proteins is required for Potato virus Y infection in tobacco plants. Journal of Virology 2007, 81:11870-11880. The authors demonstrate that J-domain proteins, CPIPs, interact with PVY CP and represent important susceptibility factors for PVY infection. Expression of dominant-negative mutants of CPIPs confers resistance to PVY.
8.
Yi G, Vaughan RC, Yarbrough I, Dharmaiah S, Kao CC: RNA binding by the brome mosaic virus capsid protein and the regulation of viral RNA accumulation. Journal of Molecular Biology 2009, 391:314-326.
22. Cho SY, Cho WK, Sohn SH, Kim KH: Interaction of the host protein NbDnaJ with Potato virus X minus-strand stem-loop 1 RNA and capsid protein affects viral replication and movement. Biochemical and Biophysical Research Communications 2012, 417:451-456. Evidence for the interaction between a J-domain protein from Nicotiana benthamiana, NbDnaJ, PVX CP and a PVX RNA element essential for viral replication and movement. PVX replication and movement are inhibited by excess NbDnaJ and accelerated in its absence.
9.
Annamalai P, Rao ALN: Packaging of brome mosaic virus subgenomic RNA is functionally coupled to replicationdependent transcription and translation of coat protein. Journal of Virology 2006, 80:10096-10108.
23. Lough TJ, Lee RH, Emerson SJ, Forster RL, Lucas WJ: Functional analysis of the 50 untranslated region of potexvirus RNA reveals a role in viral replication and cell-to-cell movement. Virology 2006, 351:455-465.
10. Neeleman L, Olsthoorn RC, Linthorst HJ, Bol JF: Translation of a nonpolyadenylated viral RNA is enhanced by binding of viral coat protein or polyadenylation of the RNA. Proceedings of the National Academy of Sciences of the United States of America 2001, 98:14286-14291. The authors show that binding of AMV CP to the 30 UTR of viral RNAs can mimic binding of the poly(A) binding protein (PABP) to the 30 poly(A) tail of cellular mRNAs. 11. Neeleman L, Linthorst HJM, Bol JF: Efficient translation of alfamovirus RNAs requires the binding of coat protein dimers to the 30 termini of the viral RNAs. Journal of General Virology 2004, 85:231-240. 12. Reichert VL, Choi M, Petrillo JE, Gehrke L: Alfalfa mosaic virus coat protein bridges RNA and RNA-dependent RNA polymerase in vitro. Virology 2007, 364:214-226. The authors show that AMV and TSV CPs enhance binding of replicase proteins to a structural element in the 30 -UTR of viral RNA. 13. Bol JF: Replication of alfamo- and ilarviruses: role of the coat protein. Annual Review of Phytopathology 2005, 43:39-62. A detailed review of the replication strategies of alfamoviruses and ilarviruses, with special emphasis on the role of CP. 14. Guogas LM, Filman DJ, Hogle JM, Gehrke L: Cofolding organizes alfalfa mosaic virus RNA and coat protein for replication. Science 2004, 306:2108-2111. Crystal structure of the AMV CP peptide-viral RNA complex reveals that, in the presence of CP, RNA assumes a highly ordered conformation essential for viral replication. Current Opinion in Virology 2012, 2:1–7
24. Tomita Y, Mizuno T, Dı´ez J, Naito S, Ahlquist P, Ishikawa M: Mutation of host DnaJ homolog inhibits brome mosaic virus negative-strand RNA synthesis. Journal of Virology 2003, 77:2990-2997. 25. Kormelink R: The molecular biology of tospoviruses and resistance strategies. In The Bunyaviridae: Molecular and Cellular Biology. Edited by Plyusnin A, Elliott RM. Horizon Scientific Press; 2011. 26. Geerts-Dimitriadou C, Lu YY, Geertsema C, Goldbach R, Kormelink R: Analysis of the Tomato spotted wilt virus ambisense S RNA-encoded hairpin structure in translation. PLoS ONE 2012, 7:e31013. 27. Trask SD, McDonald SM, Patton JT: Structural insights into the coupling of virion assembly and rotavirus replication. Nature Reviews Microbiology 2012, 10:165-177. 28. Liu H, Boulton MI, Thomas CL, Prior DA, Oparka KJ, Davies JW: Maize streak virus coat protein is karyophyllic and facilitates nuclear transport of viral DNA. Molecular Plant-Microbe Interactions 1999, 12:894-900. 29. Kunik T, Palanichelvam K, Czosnek H, Citovsky V, Gafni Y: Nuclear import of the capsid protein of tomato yellow leaf curl virus (TYLCV) in plant and insect cells. Plant Journal 1998, 13:393-399. 30. Leclerc D, Chapdelaine Y, Hohn T: Nuclear targeting of the Cauliflower mosaic virus coat protein. Journal of Virology 1999, 73:553-560. www.sciencedirect.com
Please cite this article in press as: Ivanov KI, Ma¨kinen K. Coat proteins, host factors and plant viral replication, Curr Opin Virol (2012), http://dx.doi.org/10.1016/j.coviro.2012.10.001
COVIRO-199; NO. OF PAGES 7
Coat proteins, host factors and plant viral replication Ivanov and Ma¨kinen 7
31. Karsies A, Merkle T, Szurek B, Bonas U, Hohn T, Leclerc D: Regulated nuclear targeting of Cauliflower mosaic virus. Journal of General Virology 2002, 83:1783-1790. 32. Krichevsky A, Kozlovsky SV, Gafni Y, Citovsky V: Nuclear import and export of plant virus proteins and genomes. Molecular Plant Pathology 2006, 7:131-146. A comprehensive review of the mechanisms of plant viral nuclear import and export.
early initiation step. Journal of Virology 2003, 77:511-522. 51. Lu R, Folimonov A, Shintaku M, Li WX, Falk BW, Dawson WO, Ding SW: Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:15742-15747.
33. Rhee Y, Gurel F, Gafni Y, Dingwall C, Citovsky V: A genetic system for detection of protein nuclear import and export. Nature Biotechnology 2000, 18:433-437.
52. Atabekov JG, Rodionova NP, Karpova OV, Kozlovsky SV, Novikov VK, Arkhipenko MV: Translational activation of encapsidated Potato virus X RNA by coat protein phosphorylation. Virology 2001, 286:466-474.
34. Goodin MM, Austin J, Tobias R, Fujita M, Morales C, Jackson AO: Interactions and nuclear import of the N and P proteins of sonchus yellow net virus, a plant nucleorhabdovirus. Journal of Virology 2001, 75:9393-9406.
53. Chapdelaine Y, Kirk D, Karsies A, Hohn T, Leclerc D: Mutation of capsid protein phosphorylation sites abolishes Cauliflower mosaic virus infectivity. Journal of Virology 2002, 76:1174811752.
35. Tsai CW, Redinbaugh MG, Willie KJ, Reed S, Goodin M, Hogenhout SA: Complete genome sequence and in planta subcellular localization of maize fine streak virus proteins. Journal of Virology 2005, 79:5304-5314.
54. Champagne J, Laliberte-Gagne ME, Leclerc D: Phosphorylation of the termini of Cauliflower mosaic virus precapsid protein is important for productive infection. Molecular Plant-Microbe Interactions 2007, 20:648-658.
36. Martin K, Kopperud K, Chakrabarty R, Banerjee R, Brooks R, Goodin MM: Transient expression in Nicotiana benthamiana fluorescent marker lines provides enhanced definition of protein localization, movement and interactions in planta. Plant Journal 2009, 59:150-162.
55. Ivanov KI, Puustinen P, Gabrenaite R, Vihinen H, Ro¨nnstrand L, Valmu L, Kalkkinen N, Ma¨kinen K: Phosphorylation of the potyvirus capsid protein by protein kinase CK2 and its relevance for virus infection. Plant Cell 2003, 15:2124-2139. The authors show that PVA CP is phosphorylated by the protein kinase CK2 and that mutation of a major CK2 phosphorylation site in CP renders PVA noninfectious.
37. Anderson G, Wang R, Bandyopadhyay A, Goodin M: The nucleocapsid protein of potato yellow dwarf virus: protein interactions and nuclear import mediated by a non-canonical nuclear localization signal. Frontiers in Plant Science 2012, 3:14. 38. Haupt S, Stroganova T, Ryabov E, Kim SH, Fraser G, Duncan G, Mayo MA, Barker H, Taliansky M: Nucleolar localization of potato leafroll virus capsid proteins. Journal of General Virology 2005, 86:2891-2896. 39. Olspert A, Paves H, Toomela R, Tamm T, Truve E: Cocksfoot mottle sobemovirus coat protein contains two nuclear localization signals. Virus Genes 2010, 40:423-431. 40. Scholthof HB: Plant virus transport: motions of functional equivalence. Trends in Plant Science 2005, 10:376-382. 41. Niehl A, Heinlein M: Cellular pathways for viral transport through plasmodesmata. Protoplasma 2011, 248:75-99. 42. Campbell RN: Fungal transmission of plant viruses. Annual Review of Phytopathology 1996, 34:87-108. 43. Callaway A, Giesman-Cookmeyer D, Gillock ET, Sit TL, Lommel SA: The multifunctional capsid proteins of plant RNA viruses. Annual Review of Phytopathology 2001, 39:419-460. An in-depth review of the multiple functions of plant viral CPs. 44. Bol JF: Role of capsid proteins. Methods in Molecular Biology 2008, 451:21-31. 45. Soosaar JL, Burch-Smith TM, Dinesh-Kumar SP: Mechanisms of plant resistance to viruses. Nature Reviews Microbiology 2005, 3:789-798. 46. Bendahmane A, Kanyuka K, Baulcombe DC: The Rx gene from potato controls separate virus resistance and cell death responses. Plant Cell 1999, 11:781-792. 47. Cooley MB, Pathirana S, WuF H.J., Kachroo P, Klessig DF: Members of the Arabidopsis HRT/RPP8 family of resistance genes confer resistance to both viral and oomycete pathogens. Plant Cell 2000, 12:663-676. 48. Sekine KT, Ishihara T, Hase S, Kusano T, Shah J, Takahashi H: Single amino acid alterations in Arabidopsis thaliana RCY1 compromise resistance to Cucumber mosaic virus, but differentially suppress hypersensitive response-like cell death. Plant Molecular Biology 2006, 62:669-682. 49. Thomas CL, Leh V, Lederer C, Maule AJ: Turnip crinkle virus coat protein mediates suppression of RNA silencing in Nicotiana benthamiana. Virology 2003, 306:33-41. 50. Qu F, Ren T, Morris TJ: The coat protein of turnip crinkle virus suppresses posttranscriptional gene silencing at an
www.sciencedirect.com
56. Rosario Ferna´ndez-Ferna´ndez M, Camafeita E, Bonay P, Meacute E, Albar JP, Garcı´a JA: The capsid protein of a plant single-stranded RNA virus is modified by O-linked N-acetylglucosamine. Journal of Biological Chemistry 2002, 277:135-140. 57. Chen D, Juarez S, Hartweck L, Alamillo JM, Simon-Mateo C, Perez JJ, Fernandez-Fernandez MR, Olszewski NE, Garcia JA: Identification of secret agent as the O-GlcNAc transferase that participates in Plum pox virus infection. Journal of Virology 2005, 79:9381-9387. 58. Scott CL, Hartweck LM, de Jesu´s Pe´rez J, Chen D, Garcı´a JA, Olszewski NE: SECRET AGENT, an Arabidopsis thaliana OGlcNAc transferase, modifies the Plum pox virus capsid protein. FEBS Letters 2006, 580:5829-5835. 59. Kim Y-, Udeshi ND, Balsbaugh JL, Shabanowitz J, Hunt DF, Olszewski NE: O-GlcNAcylation of the Plum pox virus capsid protein catalyzed by SECRET AGENT: characterization of OGlcNAc sites by electron transfer dissociation mass spectrometry. Amino Acids 2011, 40:869-876. 60. Zhu S, Gao F, Cao X, Chen M, Ye G, Wei C, Li Y: The rice dwarf virus P2 protein interacts with ent-kaurene oxidases in vivo, leading to reduced biosynthesis of gibberellins and rice dwarf symptoms. Plant Physiology 2005, 139:1935-1945. 61. Li Y, Wu MY, Song HH, Hu X, Qiu BS: Identification of a tobacco protein interacting with tomato mosaic virus coat protein and facilitating long-distance movement of virus. Archives of Virology 2005, 150:1993-2008. 62. Park MR, Park SH, Cho SY, Kim KH: Nicotiana benthamiana protein, NbPCIP1, interacting with Potato virus X coat protein plays a role as susceptible factor for viral infection. Virology 2009, 386:257-269. 63. Qiao Y, Li HF, Wong SM, Fan ZF: Plastocyanin transit peptide interacts with Potato virus X coat protein, while silencing of plastocyanin reduces coat protein accumulation in chloroplasts and symptom severity in host plants. Molecular Plant-Microbe Interactions 2009, 22:1523-1534. 64. Okinaka Y, Mise K, Okuno T, Furusawa I: Characterization of a novel barley protein, HCP1, that interacts with the Brome mosaic virus coat protein. Molecular Plant-Microbe Interactions 2003, 16:352-359. 65. Zhu J, Gopinath K, Murali A, Yi G, Hayward SD, Zhu H, Kao C: RNA-binding proteins that inhibit RNA virus infection. Proceedings of the National Academy of Sciences of the United States of America 2007, 104:3129-3134.
Current Opinion in Virology 2012, 2:1–7
Please cite this article in press as: Ivanov KI, Ma¨kinen K. Coat proteins, host factors and plant viral replication, Curr Opin Virol (2012), http://dx.doi.org/10.1016/j.coviro.2012.10.001