OTHER FLAVIVIRUSES
Herbert Weissenb ock
Pathology and Forensic Veterinary Medicine, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria
Most of the tick- borne and mosquito- borne flaviviruses use wild birds or mammals as hosts.
If these hosts have a co- evolutionary adaptive history with the virus, they are not affected by clinical disease. In addition to the flavivi- ruses of major importance, a few examples of flaviviruses of minor importance to wildlife populations are presented below. With one exception (Bagaza virus) none of these viruses has been detected in European wildlife. However, there is a potential for their introduction into Europe, particularly as some occur in countries bordering Europe.TICK-BORNE FLAVIVIRUSES
OMSK HEMORRHAGIC FEVER VIRUS
Omsk hemorrhagic fever virus (OHFV) is a unique species among the tick-borne flaviviruses, although it is serologically related to tick-borne encephalitis virus. The natural foci of OHFV are in the Omsk and Novosibirsk regions and also in western Siberia, which comprise forested areas and open wetlands. There were major epidemics of Omsk haemorrhagic fever (OHF) after World War II that were associated with the neglect of arable land and the explosive multiplication of Dermacentor reticulatus ticks and the narrow-skulled vole (Microtus gregalis), which are considered efficient vectors and hosts of the virus. After reestablishment of agriculture the population density of these species declined, and outbreaks of OHF became rare. A second transmission cycle that has become increasingly relevant involves the muskrat ( Ondatra zibethica) as amplifier host of OHFV. In contrast to small mammals the virus is highly pathogenic for the introduced muskrat, which develops encephalitis with high fatality rates. Muskrats are currently also the main infection source for humans, as most cases occur in hunters who acquire infection during skinning of these animals.
After experimental infection, clinical disease and death has also been observed in birds of prey, such as the marsh harrier (Circus aeruginosus), kestrel (Falco tinnunculus), long-eared owl (Asio otus) and rook ( Corvusfrugilegus). Infection of humans is characterized by a haemorrhagic fever with a generally mild course and a fatality rate between 0.5 and 3%(37).KYASANUR FOREST DISEASE VIRUS
Kyasanur Forest disease virus (KFDV) is the major tick- borne virus from southern Asia. It is geographically restricted to the Karnataka State of southern India. It causes a human febrile disease with haemorrhagic and encephalitic manifestations and a case fatality rate of up to 10%. Human cases of the disease are frequently associated with epizootics in monkeys, such as langurs (Semno- pithecus entellus) or bonnet monkeys (Macaca radiata), which may exhibit mortality rates of up to 85%. The major tick vectors belong to the genus Haemophysalis, and wild mammals, such as the Blanford rat (Rattus blanfordi), the striped forest squirrel (Funambulus tristriatus) and the house shrew (Suncus murinus) are subclinical hosts that develop high viraemia titres. A novel but closely related virus emerged in 1992 in Saudi Arabia, called Alkhurma virus (or Alkhumra virus); over 60 human cases ofAlkhurma haemorrhagic fever disease have been reported, mainly in sheep handlers and butchers, which indicates that blood or secretions from infected animals are infectious1-37).
Powassan virus
Powassan virus (POWV) is the only recognized North American member of the tick- borne flaviviruses. Owing to the low frequency of human infections (in total fewer than 50 cases), POWV is one of the less well studied of the human pathogenic flaviviruses. POWV constitutes a genetically and phenotypically diverse group of viral strains. The overall nucleotide sequence identity among all isolates of this virus species is 84% and the amino acid identity is 94%. Thus, several studies of nucleotide sequence data differentiate POWV into two distinct genetic lineages, the deer tick virus (DTV) lineage and the POWV lineage.
POWV is transmitted mainly by Ixodes (Pholeoixodes) cookei, whereas DTV is maintained by I. scapularis. POWV is apparently widely distributed in the northern hemisphere, with isolates reported from Russia, Canada and the USA. Based on serological studies, a number of vertebrates are considered to act as maintenance hosts: for example, red squirrels ( Tamiasciurus hudsonicus), chipmunks (Tamias amoenus), groundhogs (Marmota monax) or white -footed mice (Peromyscus leucopus). POWV infection of these vertebrate hosts results in a silent infection characterized by lack of clinical signs and low levels of viraemia. Clinical disease in animals is not known. Human disease is characterized by meningoencephalitis, with a case-fatality rate of approximately 10%(38).MOSQUITO-BORNE FLAVIVIRUSES
BAGAZA VIRUS
Bagaza virus (BAGV) seems to be synonymous with Israel turkey meningoencephalitis virus, which causes nonsuppurative meningoencephalitis and myocarditis in turkeys (Meleagris gallopavo^) in Israel and South Africa. In 2010, a strain of BAGV emerged in southern Spain and caused mortality of wild Galliformes (pheasants ( Phasianus colchicus); red-legged partridges (Alectoris rufa'))3'). This event recalls the permanent possibility of introduction of viruses into novel environments.
JAPANESE ENCEPHALITIS VIRUS
Japanese encephalitis virus (JEV) is the most important of the encephalitogenic flaviviruses, leading to approximately 50,000 human cases per year, with a fatality rate of up to 25%. The natural distribution range of this virus is Southeast Asia and Australasia. The vectors are Culex spp., predominantly C. tritaeniorhynchus. Virus activity is naturally maintained through bird—mosquito cycles with ardeid birds (heron family), particularly black-crowned night herons (Nycticorax nycticorax), little egrets (Egrettagarzetta), or plumed egrets (E. intermedia) as maintenance hosts. The virus does not cause disease in birds. Pigs (Sus scrofa, both domestic and feral) are important amplifying hosts and are recognized as frequent drivers of epidemic activity.
In pigs, natural infections are generally inapparent, except for occasional stillbirths and abortions when pregnant sows are infected. Experimental infection of piglets with high virus titre innoculae resulted in non-suppurative encephalitis. JEV also causes encephalitis in horses, but as with humans, horses are dead-end hosts and not involved in onward transmission. Orang-utans (Pongo pygmaeus) have also been implicated as possible vertebrate hosts in sylvatic cycles of JEV transmission in Borneo(40).ST. LOUIS encephalitis virus
Si. Louis encephalitis virus (SLEV) is distributed over most of the American continent. Birds of the orders Passeriformes and Columbiformes (perching birds and pigeon family) seem to be the major vertebrate hosts and mosquitoes from the genus Culex the principal vectors. Between 1933 and 2000 a number of epidemics with a total of at least 10,000 severe human cases including more than 1,000 fatalities were reported from several southern and mid-western US states. The last major epidemic with 222 laboratory-confirmed human cases and 11 deaths was recorded in Florida in 1990. Endemic St. Louis encephalitis affects an average of 25 individuals per year in the
USA. Infected wild birds, as well as mammals, have never been shown to develop clinical illness(41).
YELLOW FEVER VIRUS
Yellow fever virus (YFV) is estimated to be responsible for approximately 200,000 human clinical cases per year, with a case-fatality rate of approximately 20%. YFV is native to Africa, where the vast majority of cases occur. In the early 1600s, the virus was introduced to South America during the slave trade. It is maintained in an enzootic cycle involving monkeys and the canopy- dwelling mosquitoes from the genera Aedes spp. (Africa) or Haemagogus spp. (South America) in tropical rain forests. Humans may be accidentally infected (jungle yellow fever). However, the virus is periodically introduced into urban areas, where it is able to establish epidemics with Aedes aegypti as vector and with humans as the only natural host.
Although African primate species involved in the transmission cycle because of a stable host—parasite relationship show subclinical infection, many South American species, such as howler monkeys (Alouatta spp.), spider monkeys (Ateles spp.), squirrel monkeys (Saimiri spp.) or owl monkeys (Aotus spp.), may succumb to YFV infection, probably due to a comparatively short time span of co- adaptive evolution. The virus, both in humans and primates, is viscerotropic, resulting in liver damage(42).REFERENCES
1. Marra, PP,Griffing, S.M. &McLean,R.G. West Nile virus and wildlife health. Emerging Infectious Diseases. 2003;9:898-9.
2. Bakonyi, T., Ivanics, E., Erdelyi, K. et al. Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe. Emerging Infectious Diseases. 2006;12:618-23.
3. Diamond, M.S. West Nile Encephalitis Virus Infection: Viral Pathogenesis and the Host Immune Responss. Springer Science+Business Media, LLC; 2009.
4. Hubalek, Z. & Halouzka, J. West Nile fever — a reemerging mosquito- borne viral disease in Europe. Emerging Infectious Diseases. 1999;5:643- 50.
5. Reiter, P. West Nile virus in Europe: understanding the present to gauge the future. Eurosurveillance. 2010;15:19508.
6. Erdelyi, K., Ursu, K., Ferenczi, E. et al. Clinical and pathologic features of lineage 2 West Nile virus infections in birds of prey in Hungary. Vector Borne Zoonotic Diseases (Larchmont N.Y.). 2007;7:181-8.
7. Hofle, U., Blanco, J.M., Crespo, E. et al. West Nile virus in the endangered Spanish imperial eagle. Veterinary Microbiology. 2008;129:171-8.
8. Jimenez-Clavero, M.A., Sotelo, E., Fernandez-Pinero, J. et al. West Nile virus in golden eagles, Spain, 2007. Emerging Infectious Diseases. 2008;14:1489-91.
9. Malkinson, M., Banet, C., Weisman, Y. et al. Introduction of West Nile virus in the Middle East by migrating white storks. Emerging Infectious Diseases. 2000;8:392-7.
10. Hubalek, Z., Halouzka, J., Juricova, Z.
et al. Serologic survey of birds for West Nile flavivirus in southern Moravia (Czech Republic). Vector Borne Zoonotic Diseases (Larchmont N.Y). 2008;8:659-66.11. Steele, K.E., Linn, M.J., Schoepp, R.J. et al. Pathology of fatal West Nile virus infections in native and exotic birds during the 1999 outbreak in New York City, New York. Veterinary Pathology. 2000;37:208- 24.
12. Weissenbock, H., Kolodziejek, J., Url, A., Lussy, H., Rebel-Bauder, B. & Nowotny, N. Emergence of Usutu virus, an African mosquito-borne flavivirus of the Japanese encephalitis virus group, central Europe. Emerging Infectious Diseases. 2002;8:652-6.
13. Steinmetz, H.W, Bakonyi, T., Weissenbock, H. et al. Emergence and establishment of Usutu virus infection in wild and captive avian species in and around Zurich, Switzerland - genomic and pathologic comparison to other central European outbreaks. Veterinary Microbiology. 2011;148:207-12.
14. Bakonyi, T., Weissenbock, H. & Nowotny, N. Usutu virus. In: Liu, D., (ed.). Molecular Detection of Human Viral Pathogens. Boca Raton: Taylor & Francis; 2010; pp. 283-93.
15. Chvala, S., Bakonyi, T., Bukovsky, C. et al. Monitoring of Usutu virus activity and spread by using dead bird surveillance in Austria, 20032005. Veterinary Microbiology. 2007;122:237-45.
16. Manarolla, G., Bakonyi, T., Gallazzi, D. et al. Usutu virus in wild birds in northern Italy. Veterinary Microbiology. 2010;141:159-63.
17. Meister, T., Lussy, H., Bakonyi, T. et al. Serological evidence of continuing high Usutu virus (Flaviviridae) activity and establishment of herd immunity in wild birds in Austria. Veterinary Microbiology. 2008;127:237-48.
18. Busquets, N., Alba, A., Allepuz, A., Aranda, C. & Nu zn ~ez, J.I. Usutu virus sequences in Culexpipiens (Diptera: Culicidae), Spain. Emerging Infectious Diseases. 2008;14:861-3.
19. Weissenbock, H., Chvala-Mannsberger, S., Bakonyi, T. & Nowotny, N. Emergence of Usutu virus in central Europe: diagnosis, surveillance and epizootiology. In: Takken, W., Knols, B.G.J., (eds). Emerging Pests and Vector-Borne Diseases in Europe. Wageningen: Wageningen Academic Publishers; 2007; pp. 153-68.
20. Reid, H.W, Duncan, J.S., Philips, J.D.P et al. Studies on louping-ill virus (flavivirus group) in wild red grouse (Lagopus lagopus scoticuf). Journal of Hygiene, Epidemiology, Microbiology and Immunology. 1978;81:321-9.
21. Gilbert, L., Jones, L.D., Laurenson, M.K., Gould, E.A., Reid, H.W & Hudson, PJ. Ticks need not bite their red grouse hosts to infect them with louping-ill virus. Proceedings of the Royal Society of London, Series B. 2004;271 Suppl 4:S202-5.
22. Doherty, PC. & Reid, H.W. Louping-ill encephalomyelitis in the sheep. II. Distribution of virus and lesions in nervous tissue. Journal of Comparative Pathology. 1971;81:531-6.
23. Moseley, M.H., Marriott, L., Nettleton, P, Dukes, K., Irvine, RJ. & Mougeot, F. Use of real-time RT-PCR to determine the prevalence of louping-ill virus in live red grouse chicks. Veterinary Record. 2007;161: 660-1.
24. Reid, H.W. & Doherty, PC. Louping-ill encephalomyelitis in the sheep. I. The relationship of the viraemia and the antibody response to susceptibility. Journal of Comparative Pathology. 1971;81:521-9.
25. Laurenson, M.K., McKendrick, I.J., Reid, H.W, Challenor, R. & Mathewson, G.K. Prevalence, spatial distribution and the effect of control measures on louping-ill virus in the Forest of Bowland, Lancashire. Epidemiology Infection. 2007;135:963-73.
26. ICTV. International Committee on Taxonomy of Viruses. Available onlineat: http://www.ictvonline.org/virusTaxonomy.asp?version=2008. [Accessed 8 March 2012].
27. Thiel, H., Collett, M.S., Gould, E.A. et al. Flaviviridae. In: Fauquet, C.M., Mayo, M.A., Maniloff, J. et al., (eds). Virus Taxonomy: Classification and Nomenclature of Viruses. Amsterdam: Elsevier; 2005; pp. 981-98.
28. Grard, G., Moureau, G., Charrel, R.N. et al. Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy Virology. 2007;361:80-92.
29. Charrel, R.N., Attoui, H., Butenko, A.M. et al. Tick-borne virus diseases of human interest in Europe. Clinical Microbiology and Infection. 2004;10:1040-55.
30. Kocianova, E., Kozuch, O., Bakoss, P., Rehacek, J. & Kovacova, E. The prevalence of small terrestrial mammals infected with tick-borne encephalitis virus and leptospirae in the foothills of the southern Bavarian forest, Germany. Applied Parasitology. 1993;34:283-90.
31. Labuda, M., Stunzner, D., Kozuch, O. et al. Tick-borne encephalitis virus activity in Styria, Austria. Acta Virologica. 1993;37:187-90.
32. Bakhvalova, VN., Dobrotvorsky, A.K., Panov, VV., Matveeva, VA., Tkachev, S.E. & Morozova, O.V Natural tick-borne encephalitis virus infection among wild small mammals in the southeastern part of western Siberia, Russia. Vector-Borne and Zoonotic Diseases. 2006;6:32- 41.
33. Bago, Z., Bauder, B., Kolodziejek, J., Nowotny, N. & Weissenbock, H. Tickborne encephalitis in a mouflon ( Ovis ammon musimon). Veterinary Record. 2002;150:218-20.
34. Suss, J., Gelpi, E., Klaus, C. et al. Tickborne encephalitis in naturally exposed monkey (Macaca sylvanus). Emerging Infectious Diseases. 2007;13:905-7.
35. Weissenbock, H., Suchy, A. & Holzmann, H. Tick-borne encephalitis in dogs: neuropathological findings and distribution of antigen. Acta Neuropathologica. 1998;95:361-6.
36. Lindquist, L. & Vapalahti, O. Tick-borne encephalitis. Lancet. 2008;371:1861-71.
37. Dobler, G. Zoonotic tick-borne flaviviruses. Veterinary Microbiology. 2010;140:221-8.
38. Ebel, G.D. Update on Powassan virus: Emergence of a north American tick-borne flavivirus. Annual Review of Entomology. 2010;55:95-110.
39. Aguero, M., Fernandez-Pinero, J., Buitrago, D. et al. New flavivirus in Europe: Bagaza virus outbreak in partridges and pheasants in Southern Spain. International Meeting on Emerging Diseases and Surveillance; Feb. 4-7, 2011. Vienna; 2011;p. 171.
40. MacKenzie, J.S. & Williams, D.T. The zoonotic flaviviruses of southern, south-eastern and eastern Asia, and Australasia: The potential for emergent viruses. Zoo-noses and Public Health 2009;56:338-56.
41. Reisen, WK. Epidemiology of St. Louis encephalitis virus. Advances in Virus Research. 2003;61:139-83.
42. Barrett, A.D.T & Monath, T.P. Epidemiology and ecology of yellow fever virus. Advances in Virus Research. 2003;61:291-315.