- Email: [email protected]
Morbillivirus infections, with special emphasis on morbilliviruses of carnivores
Veterinary Microbiology 69 (1999) 3±13
Morbillivirus infections, with special emphasis on morbilliviruses of carnivores Tom Barrett* Institute for Animal Health, Pirbright Laboratory, Ash Road, Woking Surrey Gu24, ONF, UK
Abstract Morbilliviruses infections cause significant mortality in human beings and animals. Measles virus is responsible for up to two million childhood deaths annually in the developing world, while rinderpest and peste des petits ruminants cause severe epizootics in domestic and wild ruminants in areas of the world where they remain endemic. Canine distemper virus (CDV) is a cause of fatal disease in many species of carnivores. Distemper is controlled by vaccination in domestic dogs and farmed mink, but it may be impossible to eradicate the virus because of its global distribution and wide variety of susceptible host species, which includes both freshwater and marine seals. Research is currently under way to develop new recombinant vaccines, since the currently available live attenuated vaccines for CDV are not safe for use for all species and many valuable zoo animals need to be protected from CDV. New morbilliviruses with potentially disastrous ecological consequences for marine mammals have been discovered in the past decade; phocid distemper virus (PDV) in seals and the cetacean morbillivirus (CMV) has been found in dolphins, whales and porpoises. Reverse transcription, coupled with the polymerase chain reaction (RT/PCR) and nucleic acid sequencing, has been used to characterise the morbilliviruses and has given insights into the evolution of this virus genus. # 1999 Elsevier Science B.V. All rights reserved. Keywords: Carnivores; Morbillivirus; Epidemiology; Vaccination
1. Introduction For centuries, morbilliviruses infections have had a huge impact on both human beings and animals. Measles virus (MV), introduced by the Europeans, decimated native Americans, and it still remains a significant cause of childhood mortality, particularly in developing countries (Carmichael, 1997). The great cattle plagues of the 18th and 19th *
Tel: +44-1483-232441; fax: +44-1483-232448 E-mail address: [email protected] (T. Barrett) 0378-1135/99/$ ± see front matter # 1999 Elsevier Science B.V. All rights reserved. PII: S 0 3 7 8 - 1 1 3 5 ( 9 9 ) 0 0 0 8 0 - 2
4
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
centuries in Europe were introduced by traders from the East. Subsequently, rinderpest was introduced into Africa from India during colonial wars in Abyssinia in the 1890s, with devastating effects on the susceptible domestic and wildlife species (Mack, 1970). International campaigns are under way to eradicate globally both MV and RPV. Another morbillivirus disease of small ruminants, peste des petits ruminants virus (PPRV), is endemic in west Africa and, in recent years, has spread across the Middle East and southern Asia as far as Bangladesh (Shaila et al., 1996). In carnivores, canine distemper virus (CDV) causes serious disease in many species, both wild and domesticated. It is controlled by vaccination in domestic dogs and farmed mink, but it may be impossible to eradicate the virus because of its global distribution and wide variety of host species. New morbilliviruses with significant ecological consequences for marine mammals have been discovered in the past decade; phocid distemper virus (PDV) in seals and the cetacean morbillivirus (CMV) has been found in dolphins, whales and porpoises (Barrett et al., 1993b). 2. Virus structure When viewed through the electron microscope, morbilliviruses display the typical structures seen in other members of Paramyxoviridae. A lipid envelope encloses a helical nuculeocapsid that contains the non-segmented negative sense RNA genome. The nucleocapsids of all paramyxoviruses have a characteristic herring-bone appearance when seen through the electron microscope. Two surface glycoproteins, the hemagglutinin (H) protein and the fusion (F) protein, responsible for attachment to and fusion with the host cell membrane are embedded in the virus envelope and give it a fringed appearance. The nucleocapsid (N) protein encapsidates and protects the RNA, and two other virus proteins, the polymerase (L) protein and the phospho (P) protein, are associated with it and function in transcription and replication. The nucleotide sequence of several genes of each morbillivirus has been determined; however, the complete genome sequences of only MV, CDV and RPV viruses are known. Molecular biological techniques have been used to develop new differential diagnostic tests and to produce new candidate vaccines for these viruses, while nucleotide sequence data are being used to study virus epidemiology at the molecular level and to determine the phylogenetic relationships between the different morbilliviruses. 3. Diagnosis Conventional serological techniques and virus isolation are normally used to diagnose morbillivirus infection in samples submitted for laboratory diagnosis. However, such techniques are not suitable for use on decomposed tissue samples, which are often the only source of material available for analysis when dealing with morbillivirus infections in wild animals. The polymerase chain reaction (PCR), described by Saiki et al. (1988), has proved invaluable for analysis of such poorly preserved field samples. Since the genome of all morbilliviruses consists of a single strand of RNA, it must first be copied
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
5
into DNA, using reverse transcriptase, in a two-step reaction known as reverse transcription/polymerase chain reaction (RT-PCR). RT-PCR has been shown to be useful for the rapid detection of morbillivirus-specific RNA in samples submitted for laboratory diagnosis (Barrett et al., 1993a; Shaila et al., 1996). It has proved especially useful in identifying the new morbilliviruses found in marine mammals (Barrett et al., 1993b). Both genus-specific and universal morbillivirus primer sets have been produced that can be used to distinguish all known morbilliviruses (Forsyth and Barrett, 1995). 4. Recombinant vaccines Although live attenuated vaccines have been used successfully for many years to control morbillivirus diseases, these vaccines are not completely trouble-free. There are two distinct types of CDV vaccine, one produced in avian cells and the other in canine kidney cells, and neither is safe for use in all potential target species. CDV vaccines produced in avian cells cause disease in mink (Sutherland-Smith et al., 1997), while both types cause disease in ferrets and foxes (Carpenter et al., 1976; Henke, 1997). Vaccineinduced distemper has also been described in lesser panda (Bush et al., 1976). Since there are many potential host species kept in captivity, for which vaccination is desirable, attempts to produce new recombinant vaccines have been made by several groups. Another problem, particularly in the case of the RPV vaccine, is its sensitivity to heat inactivation. This is a serious drawback to its use in hot regions of the world where this disease still exists and an expensive cold chain is required to maintain vaccine potency. These were the main reasons for the attempts to produce safer, more robust vaccines, based on the use of poxvirus vectors to deliver the protective morbillivirus antigens (Giavedoni et al., 1991; Romero et al., 1994a, b; Yamanouchi et al., 1993). The surface glycoproteins genes of CDV, MV and RPV, have been expressed in recombinant virus vectors and have been shown to have potential as new vaccines. CDV recombinant vaccines, based on the use of either vaccinia or avipox (canarypox) viruses as vectors to express the H and F genes of CDV, have been tested successfully on dogs (Pardo et al., 1997) and ferrets (Stephenson et al., 1997). The only long-term efficacy trials on poxvirus recombinant viruses developed for morbilliviruses have been those carried out for the rinderpest±poxvirus recombinants. A major disadvantage of the recombinant vaccines has been the shorter duration of the protective immunity induced when compared with the conventional live attenuated vaccines. A rinderpest±vaccinia recombinant vaccine gave full protection from virulent virus challenge for one year (Inui et al., 1995). However, in two and three years following vaccination, only one-third of the vaccinated cattle challenged with virulent virus were found to be completely protected from disease. The other two-thirds showed mild clinical signs, but recovered fully (Yamanouchi and Barrett, unpublished observations). Similar results were obtained with a rinderpest±capripox recombinant vaccine (Ngichabe et al., 1997; Wamwayi and Barrett, unpublished observations). The short duration of immunity might not be a major problem in pet or captive animals, since booster vaccinations could be given, but it severely reduces the effectiveness of these vaccines for use in cattle in rinderpest-endemic areas.
6
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
Inactivated vaccines have proved ineffective in protecting against morbillivirus infections (Appel et al., 1984). However, some efficacy was obtained when CDV antigens were presented in association with quil A as adjuvant, i.e., as immune stimulating complexes (ISCOMS). The vaccine was shown to be capable of generating cytotoxic Tcell responses in vaccinated animals. Because of the close antigenic relationship between the different morbilliviruses, effective short-term cross-protection against heterologous virus challenge has been shown following vaccination with morbillivirus vaccines. The CDV-ISCOM vaccine protected seals from challenge with phocid distemper virus. Although sterile immunity was not achieved, the vaccinated animals showed a strong anamnestic response on challenge with PDV and were protected from clinical disease (Visser et al., 1992). Similarly, the rinderpest recombinant vaccines have been shown to cross-protect small ruminants from PPRV (Romero et al., 1995), and both MV and RPV recombinant vaccines have been shown to protect ferrets and dogs from virulent canine distemper virus infection in short-term trials (Taylor et al., 1991; Jones et al., 1997). However, the long-term practical usefulness of the vaccines in these situations is questionable. 5. Epidemiology Sequence analysis of the DNA product obtained by RT-PCR can be used to characterise morbilliviruses at the genetic level. This has enabled studies to be carried out on the molecular epidemiology of morbilliviruses, which are often difficult to isolate in tissue culture. By this means, the genetic relationships between strains of viruses from different parts of the world can be established and the likely source of new outbreaks can be traced with greater accuracy. The most devastating of the animal morbilliviruses is rinderpest and this continues to circulate in parts of Asia and Africa. Because of the implications for trade, the virus is closely monitored and molecular techniques have proved invaluable in helping to improve our understanding of the epidemiology of this virus. It is now known that three distinct lineages of RPV are currently in circulation: one lineage is confined to Asia while the other two circulate in Africa (Barrett et al., 1998). Four distinct lineages of PPRV exist, one of which was responsible for the spread of PPR across Asia in the past five years (Shaila et al., 1996). Several laboratories have reported similar studies to differentiate geographically distinct lineages of CDV in domestic and wild carnivores (Bolt et al., 1997; Haas et al., 1997). In 1992, several species of large cat died of CDV infections in American zoos (Harder et al., 1996). This outbreak was unusual as CDV was previously thought to not cause clinical disease in Felidae. In 1994, lions in Serengeti National Park, in Tanzania, died in large numbers, and CDV was identified as the cause (Harder et al., 1995). CDV appears to be an increasing problem in wildlife, perhaps because the public is more vigilant concerning wildlife, and better techniques for identifying viruses are available. During the epizootic in lions in Serengeti, several hyena cubs also died from CDV; again, the hyena was thought to not be a natural host for the virus (Haas et al., 1996). No association of CDV-induced disease with any other likely potentiating factors, such as feline immune deficiency virus, could be found (Roelke-Parker et al., 1996). It was first
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
7
Fig. 1. Phylogenetic tree based on partial nucleotide sequence data from the P gene of different geographical strains of CDV. The tree was derived using the PHYLIP DNADIST and FITCH programmes (Felsenstein, J. 1989, Phylip 3.2 Manual. University of California, Herbarium, Berkeley, California). The branch lengths are proportional to the mutational differences between the viruses and the hypothetical common ancestor that existed at the nodes in the tree.
thought that a new cat-adapted variant of CDV had emerged; however, the sequences of the viruses from cats from the two continents were very different (Harder et al., 1996). All the US isolates cluster quite closely together, while the viruses from the African lion and hyena are identical to each other, but different from the US viruses (see Fig. 1). These data indicated that local strains of CDV, and not a specially adapted feline strain of the virus, were causing the infections in the large cats and hyenas. The source of the virus in US zoo outbreaks is likely to be small carnivores, such as the racoon, that may come in contact with the captive cats. In east Africa, virus from domestic dogs, which have become increasingly numerous around the perimeter of the Serengeti National Park, are the most likely source for CDV in lion; viruses from African dogs and lions were closely related phylogenetically (Roelke-Parker et al., 1996). A recent study has shown that 55% of lions in the Massai Mara, adjacent to Serengeti, test seropositive for CDV (Kock et al., 1998). It is also unlikely that CDV is a new infection in large cats; a retrospective study carried out on samples from lions and tigers that died in Swiss zoos between 1972 and 1992, revealed that 19 out 42 samples were clearly positive for morbillivirus antigen by immunohistochemical staining and in situ hybridisation (Myers et al., 1997). CDV has become established as a disease of aquatic environments, in both marine and freshwater habitats. All pinnipeds, which are a sub-order of Carnivora, may be at serious risk from infection with CDV. This virus, and not PDV, caused the deaths of thousands of freshwater seals (Phoca sibirica) in Lake Baikal in Russia in 1987/1988 (Grachev et al., 1989) and it has been isolated from a captive seal in Canada (Lyons et al., 1993). In 1955, a mass die-off of crab-eater seals (Lobodon carcinophagus) occurred near a dog sledging base in the Antarctic. At the time, the deaths were attributed to an acute virus infection that was not further characterised. The dogs were not vaccinated against CDV and, in hindsight, it appears possible that they had passed on a CDV infection to the seals that
8
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
caused the die-off. A recent serological survey of Antarctic seals confirmed a high prevalence of CDV-specific antibodies in crab-eater seals (Bengtson et al., 1991). Since there are no terrestrial carnivores in the Antarctic, it is likely that the sledge dogs were the original source of CDV that subsequently appears to have become established in the population of crab-eater seals. The population of crab-eater seals numbers several millions, large enough to maintain a morbillivirus in circulation, and it will be interesting to study the evolution of the virus in this niche. More recently, CDV has been implicated in the deaths of Caspian seals (Phoca caspica). In June 1997, a mass die-off was observed in seals near Azerbaijan on the western shores of the Caspian Sea where several thousand seals were believed to have died. Analysis of tissue samples from one of the dead seals revealed the presence of CDV nucleic acid (Forsyth et al., 1998). The virus was different from that which caused disease in Lake Baikal seals in 1987 and from other viruses in circulation in different parts of the world. Its relationship to CDV strains from other geographical regions and to PDV is illustrated in Fig. 2. Because of their rapidly declining numbers, it is unlikely that the seal population in the Caspian Sea is capable of maintaining CDV in circulation and so it must
Fig. 2. Phylogenetic tree based on partial nucleotide sequence data from the P gene of different geographical strains of CDV and the European seal virus (PDV). The tree was derived using the PHYLIP DNADIST and FITCH programmes. The branch lengths are proportional to the mutational difference between the viruses and the hypothetical common ancestor that existed at the nodes in the tree.
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
9
have originated, as in the case of the Lake Baikal seal infections, from terrestrial carnivores. Although the virus was found in only one dead animal, and has not been established as the cause of the mass mortality in the Caspian seals, it must be considered a threat to this endangered seal population. 6. Host range Since morbilliviruses do not persist in an infectious form following an acute infection, and infection results in life-long immunity in recovered hosts, the virus relies on a constant supply of new susceptible hosts for its maintenance. It has been estimated that a population of at least 300 000 individuals is required to maintain MV in circulation (Black, 1991). Generally, each morbillivirus infects only one order of mammals to cause serious disease, e.g., MV causes disease only in primates. Non-human primates are highly susceptible to MV, but their numbers are too small to maintain the virus in circulation and infection occurs through contact with humans. When man settled in agricultural communities large enough to maintain a morbillivirus infection in circulation, a virus, such as rinderpest, must have been contracted from domesticated cattle, which then evolved into MV. CDV infects a wide range of species in the order Carnivora (Appel, 1987) and so, although each individual population may be small, there are many alternative host species to infect. There is one report of CDV in an artiodactyl, a collared peccary (Appel et al., 1991). CDV also infects pinnipeds, which form a sub-order within the order Carnivora. The full host range of PDV has been fully determined, but it can infect many species of seal (Duignan et al., 1996) and terrestrial carnivoresas well, as evidenced by the transmission of the disease to mink in the immediate vicinity of diseased seals in 1998 in Denmark (Blixenkrone-Mùller et al., 1990). Only RPV and PPRV are known to naturally infect and cause disease in artiodactyls, but dogs fed infected meat can develop antibodies to RPV, indicating a subclinical infection (Rossiter, 1994). Little is known of the host range of the cetacean morbillivirus, but serological evidence for its presence in many species of cetacean has been obtained (Duignan et al., 1995). The virus was recently isolated from monk seals in both the Mediterranean and the Atlantic (see Bildt et al., this issue) but it is disputed whether the virus, or a toxic algal bloom, caused the deaths of a large numbers of monk seals off the Mauritanian coast in 1997 (Harwood, 1998). 7. Phylogenetic relationships CDV and PDV are the two most closely related morbilliviruses and it is probable that PDV was derived from CDV (Table 1). The most likely source of infection for the European seals during the 1988 epizootic was contact with seal species from Arctic regions. This has been proposed on the grounds that morbillivirus, and more specifically PDV antibodies, were found in archival sera obtained from Arctic seals long before 1988 (Henderson et al., 1992; Ross et al., 1992). Altered migration patterns were noted in the year prior to the epizootic when harp seals (Phoca groenlandica) were seen much further
10
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
Table 1 Protein homology between phocid distemper virus (PDV) and other morbilliviruses Protein compared
CDV
MV
RPV
PPRV
N P M F H L
77 75 91 83 75 90
64 43 78 57 33 72
66 47 76 56 32 73
69 nca 77 68 36 nc
a
nc: sequence not completed yet.
south in northern European waters than usual (Dietz et al., 1989). The harp seal population is extremely large, with four million individuals in Canadian waters alone, to maintain a morbillivirus in circulation. Arctic seals may have been infected with CDV several hundreds, or several thousands, of years ago by contact with terrestrial carnivores that can carry the virus (wolves, foxes, dogs, polar bears) and have evolved into the phocid virus. As mentioned above, MV and RPV are closely related to each other and both are only distantly related to CDV, indicating that RPV is the most likely progenitor of MV. In fact, RPV has been suggested as the progenitor virus of the whole group (Norrby et al., 1985). PPRV, which is a disease of small ruminants similar to rinderpest in cattle, was originally thought to be a variant of RPV adapted to small ruminants. It is now quite clear, however, that it is a distinct virus equally distant from a theoretical morbillivirus common ancestor as the cetacean morbillivirus. The two cetacean morbillivirus isolates, from porpoise and dolphin, are very closely related, their difference being similar to the intraspecies
Fig. 3. Phylogenetic tree showing the relationships between the different morbilliviruses based on partial sequence of the P gene. The tree was derived using the PHYLIP DNADIST and FITCH programmes. The branch lengths are proportional to the mutational differences between the viruses and the hypothetical common ancestor that existed at the nodes in the tree.
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
11
variation seen in other morbilliviruses. A phylogenetic tree showing the relationships between the different morbilliviruses is shown in Fig. 3. It is likely, with increasing surveillance, that morbilliviruses will be found in other species, and techniques are now available that will allow their rapid identification and characterisation. References Appel, M.J.G., 1987. Canine distemper virus. In: Virus Infections of Vertebrates, vol. 1, Virus Infections of Carnivores, Elsevier, Amsterdam, pp. 133±159. Appel, M.J.G., Reggiardo, C., Summers, B.A., 1991. Canine distemper virus infection and ecephalitis in javelinas (collared peccaries). Arch. Virol. 119, 147±152. Appel, M.J.G., Shek, W.R., Sheshberadaran, H., Norrby, E., 1984. Measles virus and inactivated canine distemper virus induce incomplete immunity to canine distemper. Arch. Virol. 82, 73±82. Barrett, T., Amarel-Doel, C., Kitching, R.P., Gusev, A., 1993a. Use of the polymerase chain reaction in differentiating rinderpest field virus and vaccine virus in the same animals. Revue Scientifique et Technique Office International des Epizooties 12, 865±872. Barrett, T., Visser, I.K.G., Mamaev, L., Van Bressem, M.-F., Osterhaus, A.D.M.E., 1993b. Dolphin and porpoise morbilliviruses are genetically distinct from phocine distemper virus. Virology 193, 1010±1012. Barrett, T., Forsyth, M., Wamwayi, H., Kock, R., Wambula, J., Mwanzia, J., Rossiter, P., 1998. Rediscovery of the second African lineage of rinderpest virus: its epidemiological significance. Vet. Rec. 142, 669±671. Bengtson, J.L., Boveng, P., Franzen, U., Have, P., Heide Jùrgensen, M.-P., HaÈrkoÈnen, T.J., 1991. Antibodies to canine distemper virus in Antarctic seals. Mar. Mammal Sci. 71, 85±87. Black, F.L., 1991. Epidemiology of paramyxoviride. In: Kingsbury, D. (Ed.), The Paramyxoviruses, Plenum Press, New York, pp. 509±536. È rvell, C., Have, P., 1990. Phocid distemper virus Ð a threat to terrestrial Blixenkrone-Mùller, M., Svansson, V., O mammals? Vet. Rec. 127, 263±264. Bolt, G., Jensen, T.D., Gottschalcke, E., Arctander, P., Appel, M.J.G., Buckland, R., Blixenkrone-Mùller, M., 1997. Genetic diversity of the attachment (H) protein gene of current field isolates of canine distemper virus. J. Gen. Virol. 78, 367±372. Bush, M., Montali, R.J., Brownstein, D., James, A.E., Appel, M.I.G., 1976. Vaccine induced canine distemper in a lesser panda. J. Am. Vet. Med. Assoc. 169, 959±960. Carmichael, A.G., 1997. Measles: the red menace. In: Kipple, K.F. (Ed.), Plague, Pox, Pestilence, Widenfeld and Nicholson, London, pp. 80±85. Carpenter, J.W., Appel, M.J.G., Erickson, R.C., Novilla, N., 1976. Fatal vaccine-induced canine distemper virus infection in black-footed ferrets. J. Am. Vet. Med. Assoc. 169, 961±964. Dietz, R., Ansen, C.T., Have, P., Heide-Jùrgensen, M.-P., 1989. Clue to seal epizootic? Nature 338, 627. Duignan, P.J., House, C., Geraci, J.R., Early, G., Walsh, M.T., St Aubin, D.J., Koopman, H., Rhinelart, H., 1995. Morbillivirus infection in cetaceans of the western Atlantic. Vet. Microbiol. 44, 241±249. Duignan, P.J., Nielson, O., House, C., Kovacs, K.M., Duffy, N., Early, G., Sadove, S., St Aubin, D.J., Rima, B.K., Geraci, J.R., 1996. Epizootology of morbillivirus infection in harp, hooded and ringed seals from the Canadian Arctic and Western Atlantic. J. Wildl. Dis. 33, 7±19. Forsyth, M., Barrett, T., 1995. Evaluation of polymerase chain reaction for the detection of rinderpest and peste des petits ruminants viruses for epidemiological studies. Virus Res. 39, 151±163. Forsyth, M., Kennedy, S., Wilson, S., Eybatov, T., Barrett, T., 1998. Canine distemper in a Caspian seal. Vet. Rec., in press. Giavedoni, L., Jones, L., Mebus, C., Yilma, T., 1991. A vaccinia virus double recombinant expressing the F and H genes of rinderpest virus protects cattle against rinderpest and causes no pock lesions, Proc. Natl. Acad. Sci. USA 88, pp. 8011±8015. Grachev, M.A., Kumarev, V.P., Mamaev, L.V., Zorin, V.L., Baranova, L.V., Denikina, N.N., Belikov, S.I., Petrov, S.I., Petrov, E.A., Kolesnik, V.S., Kolesnik, R.S., Dorofeev, V.M., Beim, A.M., Kudelin, V.N., Magieva, F.G., Sidorov, V.N., 1989. Distemper virus in Baikal seals. Nature 338, 209.
12
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
Haas, L., Hofer, H., East, M., Wohlsein, P., Liess, B., Barrett, T., 1996. Epizootic of canine distemper virus infection in Serengeti spotted hyenas (Crocuta crocuta). Vet. Microbiol. 49, 147±152. Haas, L., Martens, W., Greiser-Wilke, I., Mamaev, L., Butina, T., Maack, D., Barrett, T., 1997. Analysis of the haemagglutinin gene of current wild-type canine distemper virus isolates from Germany. Virus Res. 48, 165± 171. Harder, T.C., Kenter, M., Appel, M.J.G., Roelke-Parker, M.E., Barrett, T., Osterhaus, A.D.M.E., 1995. Phylogenetic evidence of canine distemper virus in Serengeti's lions. Vaccine 13, 521±523. Harder, T.C., Kenter, M., Vos, H., Siebelink, K., Huisman, W., Van Amerongen, G., Orvell, C., Barrett, T., Appel, M.J.G., Osterhaus, A.D.M.E., 1996. Morbilliviruses isolated from diseased captive large fields: pathogenicity for domestic cats and comparative molecular analysis. J. Gen. Virol. 77, 397±405. Harwood, J., 1998. What killed the monk seals? Nature 393, 17±18. Henderson, G., Trudgett, A., Lyons, C., Ronald, K., 1992. Demonstration of antibodies in archival sera from Canadian seals reactive with a European isolate of phocine distemper virus. Sci. Total Environ. 115, 93±98. Henke, S.E., 1997. Effects of modified live-virus canine distemper vaccine in gray foxes. J. Wildl. Rehabil. 20, 3±7. Inui, K., Barrett, T., Kitching, R.P., Yamanouchi, K., 1995. Long term immunity in cattle vaccinated with a recombinant rinderpest vaccine. Vet. Rec. 127, 669±670. Jones, L., Tenorio, E., Gorham, J., Yilma, T., 1997. Protective vaccination of ferrets against canine distemper with recombinant pox virus vaccines expressing the H or F genes of rinderpest virus. J. Am. Vet. Res. 58, 590±593. Kock, R., Chalmers, W.S.K., Mwanzia, J., Chillingworth, C., Wambura, J., Coleman, P.G., Baxendale, W., 1998. Canine distemper in lions of the Masai Mara. Vet. Rec. 142, 662±665. Lyons, C., Welsh, M.J., Thorsen, J., Ronal, K., Rima, B.K., 1993. Canine distemper virus isolated from a captive seal. Vet. Rec. 132, 487±488. Mack, R., 1970. The great African cattle plague epidemic of the 1890s. Trop. Anim. Health and Prod. 2, 210± 219. Myers, D.L., Zurbriggen, A., Lutz, H., Pospishil, A., 1997. Distemper: not a new disease in lions and tigers. Clin. Diagn. Lab. Immunol. 4, 180±184. Ngichabe, C.K., Wamwayi, H.M., Barrett, T., Ndungu, E.K., Black, D.N., Bostock, C.J., 1997. Trial of capripoxvirus±rinderpest recombinant vaccine in African cattle. Epidemiol. Infect. 118, 63±70. Norrby, E., Sheshberadaran, H., McCollogh, K.C., 1985. Is rinderpest the archetype of the morbillivirus genus? Intervirology 23, 228±232. Pardo, M.C., Bauman, J.E., Mackowiak, M., 1997. Protection of dogs against canine distemper by vaccination with a canarypox virus recombinant expressing canine distemper fusion and haemagglutinin glycoproteins. J. Am. Vet. Res. 58, 833±836. Roelke-Parker, M.E., Munson, L., Packer, C., Kock, R., Cleaveland, S., Carpenter, M., O'Brien, S.J., Pospischil, A., Hofmann-Lehmann, R., Lutz, H., Mwamengele, G.L.M., Mgasam, N., Machange, G.A., Summers, B.A., Appel, M.J.G., 1996. A canine distemper virus epidemic in Serengeti lions (Panthera leo). Nature 379, 441± 445. Romero, C.H., Barrett, T., Chamberlain, R.W., Kitching, R.P., Fleming, M., Black, D.N., 1994a. Recombinant capripoxvirus expressing the haemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease. Virology 204, 425±429. Romero, C.H., Barrett, T., Kitching, R.P., Carn, V.M., Black, D.N., 1994b. Protection of cattle against rinderpest and lumpy skin disease with a recombinant capripoxvirus expressing the fusion protein gene of rinderpest virus. Vet. Rec. 135, 152±154. Romero, C.H., Barrett, T., Kitching, R.P., Bostock, C., Black, D.N., 1995. Protection of goats against peste des petits ruminants with recombinant capripoxviruses expressing the fusion and haemagglutinin protein genes of rinderpest virus. Vaccine 13, 36±40. Ross, P.S., Visser, I.K.G., Broeders, H.W.J., Bildt, M.W.G., Van de Bowen, W.D., Osterhaus, A.D.M.E., 1992. Antibodies to phocine distemper virus in Canadian seals. Vet. Rec. 130, 514±516. Rossiter, P.B., 1994. Rinderpest. In: Coetzer, J.A.W., Thompson, G.R., Tustin, R.C., Kriek, N.P. (Eds.), Infectious Diseases of Livestock with Special Reference to South Africa, vol. 2, Oxford University Press, Cape Town, pp. 735±757.
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
13
Saiki, R.K., Gelfand, D.H., Stoffel, S., Scharf, S.J., Higuchi, R., Horn, G.R., Mullis, K.B., Erlich, H.A., 1988. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239, 487± 491. Shaila, M.S., Shamaki, D., Forsyth, M., Diallo, A., Goatley, L., Kitching, R.P., Barrett, T., 1996. Geographic distribution and epidemiology of peste des petits ruminants viruses. Virus Res. 43, 149±153. Stephenson, C.B., Welter, J., Thanker, S.R., Taylor, J., Tartaglia, J., Paoletti, E., 1997. Canine distemper virus (CDV) infection inferrets as a model for testing morbillivirus vaccine strategies: NYVAC- and ALVACbased CDV recombinants protect against symptomatic infections. J. Virol. 71, 1506±1513. Sutherland-Smith, M.R., Rideout, B.A., Mikolon, A.B., Appel, M.J.G., Morris, P.J., Shima, A., Janssen, D.J., 1997. Vaccine-induced canine distemper in European mink, Mustela lutreola. J. Zoo Wildl. Med. 28, 312± 318. Taylor, J., Pincus, S., Tartaglia, J., Richardson, C., Alkhatib, G., Briedis, D., Appel, M.J.G., Norton, E., Paoletti, E., 1991. Vaccinia virus recombinants expressing either the measles virus fusion or haemagglutinin glycoprotein protect dogs against canine distemper virus challenge. J. Virol. 65, 4263±4274. È rvell, C., Barrett, T., Osterhaus, A.D.M.E., 1992. Canine Visser, I.K.G., Vedder, E.J., Van de Bildt, M.W.G., O distemper virus ISCOMs induce protection in harbour seals against phocid distemper but still allow subsequent infection with phocid distemper virus-1. Vaccine 10, 435±438. Yamanouchi, K., Inui, K., Sugimoto, M., Asano, K., Nishimaki, F., Kitching, R.P., Takamatsu, H., Barrett, T., 1993. Immunisation of cattle with a recombinant vaccinia vector expressing the haemagglutinin gene of rinderpest virus. Vet. Rec. 132, 152±156.
Morbillivirus infections, with special emphasis on morbilliviruses of carnivores Tom Barrett* Institute for Animal Health, Pirbright Laboratory, Ash Road, Woking Surrey Gu24, ONF, UK
Abstract Morbilliviruses infections cause significant mortality in human beings and animals. Measles virus is responsible for up to two million childhood deaths annually in the developing world, while rinderpest and peste des petits ruminants cause severe epizootics in domestic and wild ruminants in areas of the world where they remain endemic. Canine distemper virus (CDV) is a cause of fatal disease in many species of carnivores. Distemper is controlled by vaccination in domestic dogs and farmed mink, but it may be impossible to eradicate the virus because of its global distribution and wide variety of susceptible host species, which includes both freshwater and marine seals. Research is currently under way to develop new recombinant vaccines, since the currently available live attenuated vaccines for CDV are not safe for use for all species and many valuable zoo animals need to be protected from CDV. New morbilliviruses with potentially disastrous ecological consequences for marine mammals have been discovered in the past decade; phocid distemper virus (PDV) in seals and the cetacean morbillivirus (CMV) has been found in dolphins, whales and porpoises. Reverse transcription, coupled with the polymerase chain reaction (RT/PCR) and nucleic acid sequencing, has been used to characterise the morbilliviruses and has given insights into the evolution of this virus genus. # 1999 Elsevier Science B.V. All rights reserved. Keywords: Carnivores; Morbillivirus; Epidemiology; Vaccination
1. Introduction For centuries, morbilliviruses infections have had a huge impact on both human beings and animals. Measles virus (MV), introduced by the Europeans, decimated native Americans, and it still remains a significant cause of childhood mortality, particularly in developing countries (Carmichael, 1997). The great cattle plagues of the 18th and 19th *
Tel: +44-1483-232441; fax: +44-1483-232448 E-mail address: [email protected] (T. Barrett) 0378-1135/99/$ ± see front matter # 1999 Elsevier Science B.V. All rights reserved. PII: S 0 3 7 8 - 1 1 3 5 ( 9 9 ) 0 0 0 8 0 - 2
4
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
centuries in Europe were introduced by traders from the East. Subsequently, rinderpest was introduced into Africa from India during colonial wars in Abyssinia in the 1890s, with devastating effects on the susceptible domestic and wildlife species (Mack, 1970). International campaigns are under way to eradicate globally both MV and RPV. Another morbillivirus disease of small ruminants, peste des petits ruminants virus (PPRV), is endemic in west Africa and, in recent years, has spread across the Middle East and southern Asia as far as Bangladesh (Shaila et al., 1996). In carnivores, canine distemper virus (CDV) causes serious disease in many species, both wild and domesticated. It is controlled by vaccination in domestic dogs and farmed mink, but it may be impossible to eradicate the virus because of its global distribution and wide variety of host species. New morbilliviruses with significant ecological consequences for marine mammals have been discovered in the past decade; phocid distemper virus (PDV) in seals and the cetacean morbillivirus (CMV) has been found in dolphins, whales and porpoises (Barrett et al., 1993b). 2. Virus structure When viewed through the electron microscope, morbilliviruses display the typical structures seen in other members of Paramyxoviridae. A lipid envelope encloses a helical nuculeocapsid that contains the non-segmented negative sense RNA genome. The nucleocapsids of all paramyxoviruses have a characteristic herring-bone appearance when seen through the electron microscope. Two surface glycoproteins, the hemagglutinin (H) protein and the fusion (F) protein, responsible for attachment to and fusion with the host cell membrane are embedded in the virus envelope and give it a fringed appearance. The nucleocapsid (N) protein encapsidates and protects the RNA, and two other virus proteins, the polymerase (L) protein and the phospho (P) protein, are associated with it and function in transcription and replication. The nucleotide sequence of several genes of each morbillivirus has been determined; however, the complete genome sequences of only MV, CDV and RPV viruses are known. Molecular biological techniques have been used to develop new differential diagnostic tests and to produce new candidate vaccines for these viruses, while nucleotide sequence data are being used to study virus epidemiology at the molecular level and to determine the phylogenetic relationships between the different morbilliviruses. 3. Diagnosis Conventional serological techniques and virus isolation are normally used to diagnose morbillivirus infection in samples submitted for laboratory diagnosis. However, such techniques are not suitable for use on decomposed tissue samples, which are often the only source of material available for analysis when dealing with morbillivirus infections in wild animals. The polymerase chain reaction (PCR), described by Saiki et al. (1988), has proved invaluable for analysis of such poorly preserved field samples. Since the genome of all morbilliviruses consists of a single strand of RNA, it must first be copied
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
5
into DNA, using reverse transcriptase, in a two-step reaction known as reverse transcription/polymerase chain reaction (RT-PCR). RT-PCR has been shown to be useful for the rapid detection of morbillivirus-specific RNA in samples submitted for laboratory diagnosis (Barrett et al., 1993a; Shaila et al., 1996). It has proved especially useful in identifying the new morbilliviruses found in marine mammals (Barrett et al., 1993b). Both genus-specific and universal morbillivirus primer sets have been produced that can be used to distinguish all known morbilliviruses (Forsyth and Barrett, 1995). 4. Recombinant vaccines Although live attenuated vaccines have been used successfully for many years to control morbillivirus diseases, these vaccines are not completely trouble-free. There are two distinct types of CDV vaccine, one produced in avian cells and the other in canine kidney cells, and neither is safe for use in all potential target species. CDV vaccines produced in avian cells cause disease in mink (Sutherland-Smith et al., 1997), while both types cause disease in ferrets and foxes (Carpenter et al., 1976; Henke, 1997). Vaccineinduced distemper has also been described in lesser panda (Bush et al., 1976). Since there are many potential host species kept in captivity, for which vaccination is desirable, attempts to produce new recombinant vaccines have been made by several groups. Another problem, particularly in the case of the RPV vaccine, is its sensitivity to heat inactivation. This is a serious drawback to its use in hot regions of the world where this disease still exists and an expensive cold chain is required to maintain vaccine potency. These were the main reasons for the attempts to produce safer, more robust vaccines, based on the use of poxvirus vectors to deliver the protective morbillivirus antigens (Giavedoni et al., 1991; Romero et al., 1994a, b; Yamanouchi et al., 1993). The surface glycoproteins genes of CDV, MV and RPV, have been expressed in recombinant virus vectors and have been shown to have potential as new vaccines. CDV recombinant vaccines, based on the use of either vaccinia or avipox (canarypox) viruses as vectors to express the H and F genes of CDV, have been tested successfully on dogs (Pardo et al., 1997) and ferrets (Stephenson et al., 1997). The only long-term efficacy trials on poxvirus recombinant viruses developed for morbilliviruses have been those carried out for the rinderpest±poxvirus recombinants. A major disadvantage of the recombinant vaccines has been the shorter duration of the protective immunity induced when compared with the conventional live attenuated vaccines. A rinderpest±vaccinia recombinant vaccine gave full protection from virulent virus challenge for one year (Inui et al., 1995). However, in two and three years following vaccination, only one-third of the vaccinated cattle challenged with virulent virus were found to be completely protected from disease. The other two-thirds showed mild clinical signs, but recovered fully (Yamanouchi and Barrett, unpublished observations). Similar results were obtained with a rinderpest±capripox recombinant vaccine (Ngichabe et al., 1997; Wamwayi and Barrett, unpublished observations). The short duration of immunity might not be a major problem in pet or captive animals, since booster vaccinations could be given, but it severely reduces the effectiveness of these vaccines for use in cattle in rinderpest-endemic areas.
6
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
Inactivated vaccines have proved ineffective in protecting against morbillivirus infections (Appel et al., 1984). However, some efficacy was obtained when CDV antigens were presented in association with quil A as adjuvant, i.e., as immune stimulating complexes (ISCOMS). The vaccine was shown to be capable of generating cytotoxic Tcell responses in vaccinated animals. Because of the close antigenic relationship between the different morbilliviruses, effective short-term cross-protection against heterologous virus challenge has been shown following vaccination with morbillivirus vaccines. The CDV-ISCOM vaccine protected seals from challenge with phocid distemper virus. Although sterile immunity was not achieved, the vaccinated animals showed a strong anamnestic response on challenge with PDV and were protected from clinical disease (Visser et al., 1992). Similarly, the rinderpest recombinant vaccines have been shown to cross-protect small ruminants from PPRV (Romero et al., 1995), and both MV and RPV recombinant vaccines have been shown to protect ferrets and dogs from virulent canine distemper virus infection in short-term trials (Taylor et al., 1991; Jones et al., 1997). However, the long-term practical usefulness of the vaccines in these situations is questionable. 5. Epidemiology Sequence analysis of the DNA product obtained by RT-PCR can be used to characterise morbilliviruses at the genetic level. This has enabled studies to be carried out on the molecular epidemiology of morbilliviruses, which are often difficult to isolate in tissue culture. By this means, the genetic relationships between strains of viruses from different parts of the world can be established and the likely source of new outbreaks can be traced with greater accuracy. The most devastating of the animal morbilliviruses is rinderpest and this continues to circulate in parts of Asia and Africa. Because of the implications for trade, the virus is closely monitored and molecular techniques have proved invaluable in helping to improve our understanding of the epidemiology of this virus. It is now known that three distinct lineages of RPV are currently in circulation: one lineage is confined to Asia while the other two circulate in Africa (Barrett et al., 1998). Four distinct lineages of PPRV exist, one of which was responsible for the spread of PPR across Asia in the past five years (Shaila et al., 1996). Several laboratories have reported similar studies to differentiate geographically distinct lineages of CDV in domestic and wild carnivores (Bolt et al., 1997; Haas et al., 1997). In 1992, several species of large cat died of CDV infections in American zoos (Harder et al., 1996). This outbreak was unusual as CDV was previously thought to not cause clinical disease in Felidae. In 1994, lions in Serengeti National Park, in Tanzania, died in large numbers, and CDV was identified as the cause (Harder et al., 1995). CDV appears to be an increasing problem in wildlife, perhaps because the public is more vigilant concerning wildlife, and better techniques for identifying viruses are available. During the epizootic in lions in Serengeti, several hyena cubs also died from CDV; again, the hyena was thought to not be a natural host for the virus (Haas et al., 1996). No association of CDV-induced disease with any other likely potentiating factors, such as feline immune deficiency virus, could be found (Roelke-Parker et al., 1996). It was first
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
7
Fig. 1. Phylogenetic tree based on partial nucleotide sequence data from the P gene of different geographical strains of CDV. The tree was derived using the PHYLIP DNADIST and FITCH programmes (Felsenstein, J. 1989, Phylip 3.2 Manual. University of California, Herbarium, Berkeley, California). The branch lengths are proportional to the mutational differences between the viruses and the hypothetical common ancestor that existed at the nodes in the tree.
thought that a new cat-adapted variant of CDV had emerged; however, the sequences of the viruses from cats from the two continents were very different (Harder et al., 1996). All the US isolates cluster quite closely together, while the viruses from the African lion and hyena are identical to each other, but different from the US viruses (see Fig. 1). These data indicated that local strains of CDV, and not a specially adapted feline strain of the virus, were causing the infections in the large cats and hyenas. The source of the virus in US zoo outbreaks is likely to be small carnivores, such as the racoon, that may come in contact with the captive cats. In east Africa, virus from domestic dogs, which have become increasingly numerous around the perimeter of the Serengeti National Park, are the most likely source for CDV in lion; viruses from African dogs and lions were closely related phylogenetically (Roelke-Parker et al., 1996). A recent study has shown that 55% of lions in the Massai Mara, adjacent to Serengeti, test seropositive for CDV (Kock et al., 1998). It is also unlikely that CDV is a new infection in large cats; a retrospective study carried out on samples from lions and tigers that died in Swiss zoos between 1972 and 1992, revealed that 19 out 42 samples were clearly positive for morbillivirus antigen by immunohistochemical staining and in situ hybridisation (Myers et al., 1997). CDV has become established as a disease of aquatic environments, in both marine and freshwater habitats. All pinnipeds, which are a sub-order of Carnivora, may be at serious risk from infection with CDV. This virus, and not PDV, caused the deaths of thousands of freshwater seals (Phoca sibirica) in Lake Baikal in Russia in 1987/1988 (Grachev et al., 1989) and it has been isolated from a captive seal in Canada (Lyons et al., 1993). In 1955, a mass die-off of crab-eater seals (Lobodon carcinophagus) occurred near a dog sledging base in the Antarctic. At the time, the deaths were attributed to an acute virus infection that was not further characterised. The dogs were not vaccinated against CDV and, in hindsight, it appears possible that they had passed on a CDV infection to the seals that
8
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
caused the die-off. A recent serological survey of Antarctic seals confirmed a high prevalence of CDV-specific antibodies in crab-eater seals (Bengtson et al., 1991). Since there are no terrestrial carnivores in the Antarctic, it is likely that the sledge dogs were the original source of CDV that subsequently appears to have become established in the population of crab-eater seals. The population of crab-eater seals numbers several millions, large enough to maintain a morbillivirus in circulation, and it will be interesting to study the evolution of the virus in this niche. More recently, CDV has been implicated in the deaths of Caspian seals (Phoca caspica). In June 1997, a mass die-off was observed in seals near Azerbaijan on the western shores of the Caspian Sea where several thousand seals were believed to have died. Analysis of tissue samples from one of the dead seals revealed the presence of CDV nucleic acid (Forsyth et al., 1998). The virus was different from that which caused disease in Lake Baikal seals in 1987 and from other viruses in circulation in different parts of the world. Its relationship to CDV strains from other geographical regions and to PDV is illustrated in Fig. 2. Because of their rapidly declining numbers, it is unlikely that the seal population in the Caspian Sea is capable of maintaining CDV in circulation and so it must
Fig. 2. Phylogenetic tree based on partial nucleotide sequence data from the P gene of different geographical strains of CDV and the European seal virus (PDV). The tree was derived using the PHYLIP DNADIST and FITCH programmes. The branch lengths are proportional to the mutational difference between the viruses and the hypothetical common ancestor that existed at the nodes in the tree.
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
9
have originated, as in the case of the Lake Baikal seal infections, from terrestrial carnivores. Although the virus was found in only one dead animal, and has not been established as the cause of the mass mortality in the Caspian seals, it must be considered a threat to this endangered seal population. 6. Host range Since morbilliviruses do not persist in an infectious form following an acute infection, and infection results in life-long immunity in recovered hosts, the virus relies on a constant supply of new susceptible hosts for its maintenance. It has been estimated that a population of at least 300 000 individuals is required to maintain MV in circulation (Black, 1991). Generally, each morbillivirus infects only one order of mammals to cause serious disease, e.g., MV causes disease only in primates. Non-human primates are highly susceptible to MV, but their numbers are too small to maintain the virus in circulation and infection occurs through contact with humans. When man settled in agricultural communities large enough to maintain a morbillivirus infection in circulation, a virus, such as rinderpest, must have been contracted from domesticated cattle, which then evolved into MV. CDV infects a wide range of species in the order Carnivora (Appel, 1987) and so, although each individual population may be small, there are many alternative host species to infect. There is one report of CDV in an artiodactyl, a collared peccary (Appel et al., 1991). CDV also infects pinnipeds, which form a sub-order within the order Carnivora. The full host range of PDV has been fully determined, but it can infect many species of seal (Duignan et al., 1996) and terrestrial carnivoresas well, as evidenced by the transmission of the disease to mink in the immediate vicinity of diseased seals in 1998 in Denmark (Blixenkrone-Mùller et al., 1990). Only RPV and PPRV are known to naturally infect and cause disease in artiodactyls, but dogs fed infected meat can develop antibodies to RPV, indicating a subclinical infection (Rossiter, 1994). Little is known of the host range of the cetacean morbillivirus, but serological evidence for its presence in many species of cetacean has been obtained (Duignan et al., 1995). The virus was recently isolated from monk seals in both the Mediterranean and the Atlantic (see Bildt et al., this issue) but it is disputed whether the virus, or a toxic algal bloom, caused the deaths of a large numbers of monk seals off the Mauritanian coast in 1997 (Harwood, 1998). 7. Phylogenetic relationships CDV and PDV are the two most closely related morbilliviruses and it is probable that PDV was derived from CDV (Table 1). The most likely source of infection for the European seals during the 1988 epizootic was contact with seal species from Arctic regions. This has been proposed on the grounds that morbillivirus, and more specifically PDV antibodies, were found in archival sera obtained from Arctic seals long before 1988 (Henderson et al., 1992; Ross et al., 1992). Altered migration patterns were noted in the year prior to the epizootic when harp seals (Phoca groenlandica) were seen much further
10
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
Table 1 Protein homology between phocid distemper virus (PDV) and other morbilliviruses Protein compared
CDV
MV
RPV
PPRV
N P M F H L
77 75 91 83 75 90
64 43 78 57 33 72
66 47 76 56 32 73
69 nca 77 68 36 nc
a
nc: sequence not completed yet.
south in northern European waters than usual (Dietz et al., 1989). The harp seal population is extremely large, with four million individuals in Canadian waters alone, to maintain a morbillivirus in circulation. Arctic seals may have been infected with CDV several hundreds, or several thousands, of years ago by contact with terrestrial carnivores that can carry the virus (wolves, foxes, dogs, polar bears) and have evolved into the phocid virus. As mentioned above, MV and RPV are closely related to each other and both are only distantly related to CDV, indicating that RPV is the most likely progenitor of MV. In fact, RPV has been suggested as the progenitor virus of the whole group (Norrby et al., 1985). PPRV, which is a disease of small ruminants similar to rinderpest in cattle, was originally thought to be a variant of RPV adapted to small ruminants. It is now quite clear, however, that it is a distinct virus equally distant from a theoretical morbillivirus common ancestor as the cetacean morbillivirus. The two cetacean morbillivirus isolates, from porpoise and dolphin, are very closely related, their difference being similar to the intraspecies
Fig. 3. Phylogenetic tree showing the relationships between the different morbilliviruses based on partial sequence of the P gene. The tree was derived using the PHYLIP DNADIST and FITCH programmes. The branch lengths are proportional to the mutational differences between the viruses and the hypothetical common ancestor that existed at the nodes in the tree.
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
11
variation seen in other morbilliviruses. A phylogenetic tree showing the relationships between the different morbilliviruses is shown in Fig. 3. It is likely, with increasing surveillance, that morbilliviruses will be found in other species, and techniques are now available that will allow their rapid identification and characterisation. References Appel, M.J.G., 1987. Canine distemper virus. In: Virus Infections of Vertebrates, vol. 1, Virus Infections of Carnivores, Elsevier, Amsterdam, pp. 133±159. Appel, M.J.G., Reggiardo, C., Summers, B.A., 1991. Canine distemper virus infection and ecephalitis in javelinas (collared peccaries). Arch. Virol. 119, 147±152. Appel, M.J.G., Shek, W.R., Sheshberadaran, H., Norrby, E., 1984. Measles virus and inactivated canine distemper virus induce incomplete immunity to canine distemper. Arch. Virol. 82, 73±82. Barrett, T., Amarel-Doel, C., Kitching, R.P., Gusev, A., 1993a. Use of the polymerase chain reaction in differentiating rinderpest field virus and vaccine virus in the same animals. Revue Scientifique et Technique Office International des Epizooties 12, 865±872. Barrett, T., Visser, I.K.G., Mamaev, L., Van Bressem, M.-F., Osterhaus, A.D.M.E., 1993b. Dolphin and porpoise morbilliviruses are genetically distinct from phocine distemper virus. Virology 193, 1010±1012. Barrett, T., Forsyth, M., Wamwayi, H., Kock, R., Wambula, J., Mwanzia, J., Rossiter, P., 1998. Rediscovery of the second African lineage of rinderpest virus: its epidemiological significance. Vet. Rec. 142, 669±671. Bengtson, J.L., Boveng, P., Franzen, U., Have, P., Heide Jùrgensen, M.-P., HaÈrkoÈnen, T.J., 1991. Antibodies to canine distemper virus in Antarctic seals. Mar. Mammal Sci. 71, 85±87. Black, F.L., 1991. Epidemiology of paramyxoviride. In: Kingsbury, D. (Ed.), The Paramyxoviruses, Plenum Press, New York, pp. 509±536. È rvell, C., Have, P., 1990. Phocid distemper virus Ð a threat to terrestrial Blixenkrone-Mùller, M., Svansson, V., O mammals? Vet. Rec. 127, 263±264. Bolt, G., Jensen, T.D., Gottschalcke, E., Arctander, P., Appel, M.J.G., Buckland, R., Blixenkrone-Mùller, M., 1997. Genetic diversity of the attachment (H) protein gene of current field isolates of canine distemper virus. J. Gen. Virol. 78, 367±372. Bush, M., Montali, R.J., Brownstein, D., James, A.E., Appel, M.I.G., 1976. Vaccine induced canine distemper in a lesser panda. J. Am. Vet. Med. Assoc. 169, 959±960. Carmichael, A.G., 1997. Measles: the red menace. In: Kipple, K.F. (Ed.), Plague, Pox, Pestilence, Widenfeld and Nicholson, London, pp. 80±85. Carpenter, J.W., Appel, M.J.G., Erickson, R.C., Novilla, N., 1976. Fatal vaccine-induced canine distemper virus infection in black-footed ferrets. J. Am. Vet. Med. Assoc. 169, 961±964. Dietz, R., Ansen, C.T., Have, P., Heide-Jùrgensen, M.-P., 1989. Clue to seal epizootic? Nature 338, 627. Duignan, P.J., House, C., Geraci, J.R., Early, G., Walsh, M.T., St Aubin, D.J., Koopman, H., Rhinelart, H., 1995. Morbillivirus infection in cetaceans of the western Atlantic. Vet. Microbiol. 44, 241±249. Duignan, P.J., Nielson, O., House, C., Kovacs, K.M., Duffy, N., Early, G., Sadove, S., St Aubin, D.J., Rima, B.K., Geraci, J.R., 1996. Epizootology of morbillivirus infection in harp, hooded and ringed seals from the Canadian Arctic and Western Atlantic. J. Wildl. Dis. 33, 7±19. Forsyth, M., Barrett, T., 1995. Evaluation of polymerase chain reaction for the detection of rinderpest and peste des petits ruminants viruses for epidemiological studies. Virus Res. 39, 151±163. Forsyth, M., Kennedy, S., Wilson, S., Eybatov, T., Barrett, T., 1998. Canine distemper in a Caspian seal. Vet. Rec., in press. Giavedoni, L., Jones, L., Mebus, C., Yilma, T., 1991. A vaccinia virus double recombinant expressing the F and H genes of rinderpest virus protects cattle against rinderpest and causes no pock lesions, Proc. Natl. Acad. Sci. USA 88, pp. 8011±8015. Grachev, M.A., Kumarev, V.P., Mamaev, L.V., Zorin, V.L., Baranova, L.V., Denikina, N.N., Belikov, S.I., Petrov, S.I., Petrov, E.A., Kolesnik, V.S., Kolesnik, R.S., Dorofeev, V.M., Beim, A.M., Kudelin, V.N., Magieva, F.G., Sidorov, V.N., 1989. Distemper virus in Baikal seals. Nature 338, 209.
12
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
Haas, L., Hofer, H., East, M., Wohlsein, P., Liess, B., Barrett, T., 1996. Epizootic of canine distemper virus infection in Serengeti spotted hyenas (Crocuta crocuta). Vet. Microbiol. 49, 147±152. Haas, L., Martens, W., Greiser-Wilke, I., Mamaev, L., Butina, T., Maack, D., Barrett, T., 1997. Analysis of the haemagglutinin gene of current wild-type canine distemper virus isolates from Germany. Virus Res. 48, 165± 171. Harder, T.C., Kenter, M., Appel, M.J.G., Roelke-Parker, M.E., Barrett, T., Osterhaus, A.D.M.E., 1995. Phylogenetic evidence of canine distemper virus in Serengeti's lions. Vaccine 13, 521±523. Harder, T.C., Kenter, M., Vos, H., Siebelink, K., Huisman, W., Van Amerongen, G., Orvell, C., Barrett, T., Appel, M.J.G., Osterhaus, A.D.M.E., 1996. Morbilliviruses isolated from diseased captive large fields: pathogenicity for domestic cats and comparative molecular analysis. J. Gen. Virol. 77, 397±405. Harwood, J., 1998. What killed the monk seals? Nature 393, 17±18. Henderson, G., Trudgett, A., Lyons, C., Ronald, K., 1992. Demonstration of antibodies in archival sera from Canadian seals reactive with a European isolate of phocine distemper virus. Sci. Total Environ. 115, 93±98. Henke, S.E., 1997. Effects of modified live-virus canine distemper vaccine in gray foxes. J. Wildl. Rehabil. 20, 3±7. Inui, K., Barrett, T., Kitching, R.P., Yamanouchi, K., 1995. Long term immunity in cattle vaccinated with a recombinant rinderpest vaccine. Vet. Rec. 127, 669±670. Jones, L., Tenorio, E., Gorham, J., Yilma, T., 1997. Protective vaccination of ferrets against canine distemper with recombinant pox virus vaccines expressing the H or F genes of rinderpest virus. J. Am. Vet. Res. 58, 590±593. Kock, R., Chalmers, W.S.K., Mwanzia, J., Chillingworth, C., Wambura, J., Coleman, P.G., Baxendale, W., 1998. Canine distemper in lions of the Masai Mara. Vet. Rec. 142, 662±665. Lyons, C., Welsh, M.J., Thorsen, J., Ronal, K., Rima, B.K., 1993. Canine distemper virus isolated from a captive seal. Vet. Rec. 132, 487±488. Mack, R., 1970. The great African cattle plague epidemic of the 1890s. Trop. Anim. Health and Prod. 2, 210± 219. Myers, D.L., Zurbriggen, A., Lutz, H., Pospishil, A., 1997. Distemper: not a new disease in lions and tigers. Clin. Diagn. Lab. Immunol. 4, 180±184. Ngichabe, C.K., Wamwayi, H.M., Barrett, T., Ndungu, E.K., Black, D.N., Bostock, C.J., 1997. Trial of capripoxvirus±rinderpest recombinant vaccine in African cattle. Epidemiol. Infect. 118, 63±70. Norrby, E., Sheshberadaran, H., McCollogh, K.C., 1985. Is rinderpest the archetype of the morbillivirus genus? Intervirology 23, 228±232. Pardo, M.C., Bauman, J.E., Mackowiak, M., 1997. Protection of dogs against canine distemper by vaccination with a canarypox virus recombinant expressing canine distemper fusion and haemagglutinin glycoproteins. J. Am. Vet. Res. 58, 833±836. Roelke-Parker, M.E., Munson, L., Packer, C., Kock, R., Cleaveland, S., Carpenter, M., O'Brien, S.J., Pospischil, A., Hofmann-Lehmann, R., Lutz, H., Mwamengele, G.L.M., Mgasam, N., Machange, G.A., Summers, B.A., Appel, M.J.G., 1996. A canine distemper virus epidemic in Serengeti lions (Panthera leo). Nature 379, 441± 445. Romero, C.H., Barrett, T., Chamberlain, R.W., Kitching, R.P., Fleming, M., Black, D.N., 1994a. Recombinant capripoxvirus expressing the haemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease. Virology 204, 425±429. Romero, C.H., Barrett, T., Kitching, R.P., Carn, V.M., Black, D.N., 1994b. Protection of cattle against rinderpest and lumpy skin disease with a recombinant capripoxvirus expressing the fusion protein gene of rinderpest virus. Vet. Rec. 135, 152±154. Romero, C.H., Barrett, T., Kitching, R.P., Bostock, C., Black, D.N., 1995. Protection of goats against peste des petits ruminants with recombinant capripoxviruses expressing the fusion and haemagglutinin protein genes of rinderpest virus. Vaccine 13, 36±40. Ross, P.S., Visser, I.K.G., Broeders, H.W.J., Bildt, M.W.G., Van de Bowen, W.D., Osterhaus, A.D.M.E., 1992. Antibodies to phocine distemper virus in Canadian seals. Vet. Rec. 130, 514±516. Rossiter, P.B., 1994. Rinderpest. In: Coetzer, J.A.W., Thompson, G.R., Tustin, R.C., Kriek, N.P. (Eds.), Infectious Diseases of Livestock with Special Reference to South Africa, vol. 2, Oxford University Press, Cape Town, pp. 735±757.
T. Barrett / Veterinary Microbiology 69 (1999) 3±13
13
Saiki, R.K., Gelfand, D.H., Stoffel, S., Scharf, S.J., Higuchi, R., Horn, G.R., Mullis, K.B., Erlich, H.A., 1988. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239, 487± 491. Shaila, M.S., Shamaki, D., Forsyth, M., Diallo, A., Goatley, L., Kitching, R.P., Barrett, T., 1996. Geographic distribution and epidemiology of peste des petits ruminants viruses. Virus Res. 43, 149±153. Stephenson, C.B., Welter, J., Thanker, S.R., Taylor, J., Tartaglia, J., Paoletti, E., 1997. Canine distemper virus (CDV) infection inferrets as a model for testing morbillivirus vaccine strategies: NYVAC- and ALVACbased CDV recombinants protect against symptomatic infections. J. Virol. 71, 1506±1513. Sutherland-Smith, M.R., Rideout, B.A., Mikolon, A.B., Appel, M.J.G., Morris, P.J., Shima, A., Janssen, D.J., 1997. Vaccine-induced canine distemper in European mink, Mustela lutreola. J. Zoo Wildl. Med. 28, 312± 318. Taylor, J., Pincus, S., Tartaglia, J., Richardson, C., Alkhatib, G., Briedis, D., Appel, M.J.G., Norton, E., Paoletti, E., 1991. Vaccinia virus recombinants expressing either the measles virus fusion or haemagglutinin glycoprotein protect dogs against canine distemper virus challenge. J. Virol. 65, 4263±4274. È rvell, C., Barrett, T., Osterhaus, A.D.M.E., 1992. Canine Visser, I.K.G., Vedder, E.J., Van de Bildt, M.W.G., O distemper virus ISCOMs induce protection in harbour seals against phocid distemper but still allow subsequent infection with phocid distemper virus-1. Vaccine 10, 435±438. Yamanouchi, K., Inui, K., Sugimoto, M., Asano, K., Nishimaki, F., Kitching, R.P., Takamatsu, H., Barrett, T., 1993. Immunisation of cattle with a recombinant vaccinia vector expressing the haemagglutinin gene of rinderpest virus. Vet. Rec. 132, 152±156.