Table of Contents
ISRN Virology
Volume 2013 (2013), Article ID 861912, 22 pages
http://dx.doi.org/10.5402/2013/861912
Review Article

The Pathogenesis of Alphaviruses

Department of Microbiology, Moyne Institute, Trinity College, Dublin 2, Ireland

Received 27 September 2012; Accepted 19 October 2012

Academic Editors: B. Kim and J. S. Lee

Copyright © 2013 Gregory J. Atkins. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. H. Strauss and E. G. Strauss, “The alphaviruses: gene expression, replication, and evolution,” Microbiological Reviews, vol. 58, no. 3, pp. 491–562, 1994. View at Google Scholar · View at Scopus
  2. B. Levine, Q. Huang, J. T. Isaacs, J. C. Reed, D. E. Griffin, and J. M. Hardwick, “Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene,” Nature, vol. 361, no. 6414, pp. 739–742, 1993. View at Publisher · View at Google Scholar · View at Scopus
  3. V. E. Nava, A. Rosen, M. A. Veliuona, R. J. Clem, B. Levine, and J. M. Hardwick, “Sindbis virus induces apoptosis through a caspase-dependent, CrmA- sensitive pathway,” Journal of Virology, vol. 72, no. 1, pp. 452–459, 1998. View at Google Scholar · View at Scopus
  4. J. T. Jan and D. E. Griffin, “Induction of apoptosis by sindbis virus occurs at cell entry and does not require virus replication,” Journal of Virology, vol. 73, no. 12, pp. 10296–10302, 1999. View at Google Scholar · View at Scopus
  5. G. M. Glasgow, M. M. McGee, B. J. Sheahan, and G. J. Atkins, “Death mechanisms in cultured cells infected by Semliki Forest virus,” Journal of General Virology, vol. 78, no. 7, pp. 1559–1563, 1997. View at Google Scholar · View at Scopus
  6. G. M. Glasgow, M. M. McGee, C. J. Tarbatt, D. A. Mooney, B. J. Sheahan, and G. J. Atkins, “The Semliki Forest virus vector induces p53-independent apoptosis,” Journal of General Virology, vol. 79, no. 10, pp. 2405–2410, 1998. View at Google Scholar · View at Scopus
  7. H. Wang, C. D. Blair, K. E. Olson, and R. J. Clem, “Effects of inducing or inhibiting apoptosis on Sindbis virus replication in mosquito cells,” Journal of General Virology, vol. 89, no. 11, pp. 2651–2661, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. A. R. Karpf and D. T. Brown, “Comparison of Sindbis virus-induced pathology in mosquito and vertebrate cell cultures,” Virology, vol. 240, no. 2, pp. 193–201, 1998. View at Publisher · View at Google Scholar · View at Scopus
  9. J. O. Lundström, “Mosquito-borne viruses in Western Europe: a review,” Journal of Vector Ecology, vol. 24, no. 1, pp. 1–39, 1999. View at Google Scholar · View at Scopus
  10. J. Sane, S. Kurkela, N. Putkuri, E. Huhtamo, A. Vaheri, and O. Vapalahti, “Complete coding sequence and molecular epidemiological analysis of Sindbis virus isolates from mosquitoes and humans, Finland,” Journal of General Virology, vol. 93, pp. 1984–1990, 2012. View at Google Scholar
  11. H. Jöst, A. Bialonski, V. Storch, S. Günther, N. Becker, and J. Schmidt-Chanasit, “Isolation and phylogenetic analysis of sindbis viruses from mosquitoes in Germany,” Journal of Clinical Microbiology, vol. 48, no. 5, pp. 1900–1903, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Lustig, A. C. Jackson, C. S. Hahn, D. E. Griffin, E. G. Strauss, and J. H. Strauss, “Molecular basis of Sindbis virus neurovirulence in mice,” Journal of Virology, vol. 62, no. 7, pp. 2329–2336, 1988. View at Google Scholar · View at Scopus
  13. P. Lee, R. Knight, J. M. Smit, J. Wilschut, and D. E. Griffin, “A single mutation in the E2 glycoprotein important for neurovirulence influences binding of Sindbis virus to neuroblastoma cells,” Journal of Virology, vol. 76, no. 12, pp. 6302–6310, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. P. C. Tucker, E. G. Strauss, R. J. Kuhn, J. H. Strauss, and D. E. Griffin, “Viral determinants of age-dependent virulence of sindbis virus for mice,” Journal of Virology, vol. 67, no. 8, pp. 4605–4610, 1993. View at Google Scholar · View at Scopus
  15. L. K. Dropulic, J. M. Hardwick, and D. E. Griffin, “A single amino acid change in the E2 glycoprotein of sindbis virus confers neurovirulence by altering an early step of virus replication,” Journal of Virology, vol. 71, no. 8, pp. 6100–6105, 1997. View at Google Scholar · View at Scopus
  16. P. C. Tucker, S. H. Lee, N. Bui, D. Martinie, and D. E. Griffin, “Amino acid changes in the sindbis virus E2 glycoprotein that increase neurovirulence improve entry into neuroblastoma cells,” Journal of Virology, vol. 71, no. 8, pp. 6106–6112, 1997. View at Google Scholar · View at Scopus
  17. J. M. Polo, N. L. Davis, C. M. Rice, H. V. Huang, and R. E. Johnston, “Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro,” Journal of Virology, vol. 62, no. 6, pp. 2124–2133, 1988. View at Google Scholar · View at Scopus
  18. J. Dubuisson, S. Lustig, N. Ruggli, Y. Akov, and C. M. Rice, “Genetic determinants of Sindbis virus neuroinvasiveness,” Journal of Virology, vol. 71, no. 4, pp. 2636–2646, 1997. View at Google Scholar · View at Scopus
  19. M. S. Suthar, R. Shabman, K. Madric, C. Lambeth, and M. T. Heise, “Identification of adult mouse neurovirulence determinants of the Sindbis virus strain AR86,” Journal of Virology, vol. 79, no. 7, pp. 4219–4228, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. D. E. Griffin, B. Levine, W. R. Tyor, and D. N. Irani, “The immune response in viral encephalitis,” Seminars in Immunology, vol. 4, no. 2, pp. 111–119, 1992. View at Google Scholar · View at Scopus
  21. T. U. Metcalf and D. E. Griffin, “Alphavirus-induced encephalomyelitis: antibody-secreting cells and viral clearance from the nervous system,” Journal of Virology, vol. 85, pp. 11490–11501, 2011. View at Google Scholar
  22. R. Burdeinick-Kerr, J. Wind, and D. E. Griffin, “Synergistic roles of antibody and interferon in noncytolytic clearance of Sindbis virus from different regions of the central nervous system,” Journal of Virology, vol. 81, no. 11, pp. 5628–5636, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. G. K. Binder and D. E. Griffin, “Interferon-γ-mediated site-specific clearance of alphavirus from CNS neurons,” Science, vol. 293, no. 5528, pp. 303–306, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Kimura and D. E. Griffin, “The role of CD8+ T cells and major histocompatibility complex class I expression in the central nervous system of mice infected with neurovirulent Sindbis virus,” Journal of Virology, vol. 74, no. 13, pp. 6117–6125, 2000. View at Publisher · View at Google Scholar · View at Scopus
  25. I. P. Greene, E. Y. Lee, N. Prow, B. Ngwang, and D. E. Griffin, “Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 9, pp. 3575–3580, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Kimura and D. E. Griffin, “Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus,” Virology, vol. 311, no. 1, pp. 28–39, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. D. E. Griffin, “Recovery from viral encephalomyelitis: immune-mediated noncytolytic virus clearance from neurons,” Immunologic Research, vol. 47, no. 1–3, pp. 123–133, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. P. S. Vernon and D. E. Griffin, “Characterization of an in vitro model of alphavirus infection of immature and mature neurons,” Journal of Virology, vol. 79, no. 6, pp. 3438–3447, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Burdeinick-Kerr and D. E. Griffin, “Gamma interferon-dependent, noncytolytic clearance of sindbis virus infection from neurons in vitro,” Journal of Virology, vol. 79, no. 9, pp. 5374–5385, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. R. Burdeinick-Kerr, D. Govindarajan, and D. E. Griffin, “Noncytolytic clearance of sindbis virus infection from neurons by gamma interferon is dependent on Jak/Stat signaling,” Journal of Virology, vol. 83, no. 8, pp. 3429–3435, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. J. D. Simmons, A. C. Wollish, and M. T. Heise, “A determinant of sindbis virus neurovirulence enables efficient disruption of Jak/STAT signaling,” Journal of Virology, vol. 84, no. 21, pp. 11429–11439, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Lewis, S. L. Wesselingh, D. E. Griffin, and J. Marie Hardwick, “Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence,” Journal of Virology, vol. 70, no. 3, pp. 1828–1835, 1996. View at Google Scholar · View at Scopus
  33. S. Ubol, P. C. Tucker, D. E. Griffin, and J. M. Hardwick, “Neurovirulent strains of Alphavirus induce apoptosis in bcl-2-expressing cells: role of a single amino acid change in the E2 glycoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 11, pp. 5202–5206, 1994. View at Publisher · View at Google Scholar · View at Scopus
  34. J. Lewis, G. A. Oyler, K. Ueno et al., “Inhibition of virus-induced neuronal apoptosis by Bax,” Nature Medicine, vol. 5, no. 7, pp. 832–835, 1999. View at Publisher · View at Google Scholar · View at Scopus
  35. D. A. Kerr, T. Larsen, S. H. Cook et al., “BCL-2 and BAX protect adult mice from lethal Sindbis virus infection but do not protect spinal cord motor neurons or prevent paralysis,” Journal of Virology, vol. 76, no. 20, pp. 10393–10400, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. A. R. Karpf, J. M. Blake, and D. T. Brown, “Characterization of the infection of Aedes albopictus cell clones by Sindbis virus,” Virus Research, vol. 50, no. 1, pp. 1–13, 1997. View at Publisher · View at Google Scholar · View at Scopus
  37. U. Mudiganti, R. Hernandez, D. Ferreira, and D. T. Brown, “Sindbis virus infection of two model insect cell systems-A comparative study,” Virus Research, vol. 122, no. 1-2, pp. 28–34, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. D. F. Bowers, C. G. Coleman, and D. T. Brown, “Sindbis virus-associated pathology in Aedes albopictus (Diptera: Culicidae),” Journal of Medical Entomology, vol. 40, no. 5, pp. 698–705, 2003. View at Google Scholar · View at Scopus
  39. K. M. Myles, D. J. Pierro, and K. E. Olson, “Deletions in the putative cell receptor-binding domain of sindbis virus strain MRE16 E2 glycoprotein reduce midgut infectivity in Aedes aegypti,” Journal of Virology, vol. 77, no. 16, pp. 8872–8881, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. D. J. Pierro, E. L. Powers, and K. E. Olson, “Genetic determinants of Sindbis virus strain TR339 affecting midgut infection in the mosquito Aedes aegypti,” Journal of General Virology, vol. 88, no. 5, pp. 1545–1554, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. D. J. Pierro, E. L. Powers, and K. E. Olson, “Genetic determinants of Sindbis virus mosquito infection are associated with a highly conserved alphavirus and flavivirus envelope sequence,” Journal of Virology, vol. 82, no. 6, pp. 2966–2974, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. K. M. Myles, M. R. Wiley, E. M. Morazzani, and Z. N. Adelman, “Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 50, pp. 19938–19943, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. K. C. Smithburn and W. J. Haddow, “Semliki Forest virus—I—isolation and pathogenic properties,” Journal of Immunology, vol. 49, pp. 141–145, 1944. View at Google Scholar
  44. K. C. Smithburn, A. J. Haddow, and A. F. Mahaffy, “A neurotropic virus isolated from Aedes mosquitoes caught in the Semliki forest,” American Journal of Tropical Medicine and Hygiene, vol. 26, pp. 189–208, 1946. View at Google Scholar
  45. C. C. Mathiot, G. Grimaud, P. Garry et al., “An outbreak of human semliki forest virus infections in Central African Republic,” American Journal of Tropical Medicine and Hygiene, vol. 42, no. 4, pp. 386–393, 1990. View at Google Scholar · View at Scopus
  46. W. R. Willems, G. Kaluza, and C. B. Boschek, “Semliki Forest virus: cause of a fatal case of human encephalitis,” Science, vol. 203, no. 4385, pp. 1127–1129, 1979. View at Google Scholar · View at Scopus
  47. C. J. Bradish, K. Allner, and H. B. Maber, “The virulence of original and derived strains of Semliki forest virus for mice, guinea-pigs and rabbits,” Journal of General Virology, vol. 12, no. 2, pp. 141–160, 1971. View at Google Scholar · View at Scopus
  48. B. M. McIntosh, C. Brooke Worth, and R. H. Kokernot, “Isolation of semliki forest virus from Aedes (Aedimorphus) argenteopunctatus (theobald) collected in Portuguese East Africa,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 55, no. 2, pp. 192–198, 1961. View at Google Scholar · View at Scopus
  49. M. C. Gates, B. J. Sheahan, and G. J. Atkins, “The pathogenicity of the M9 mutant of Semliki Forest virus in immune-compromised mice,” Journal of General Virology, vol. 65, no. 1, pp. 73–80, 1984. View at Google Scholar · View at Scopus
  50. G. M. Glasgow, B. J. Sheahan, G. J. Atkins, J. M. Wahlberg, A. Salminen, and P. Liljestrom, “Two mutations in the envelope glycoprotein E2 of Semliki Forest virus affecting the maturation and entry patterns of the virus alter pathogenicity for mice,” Virology, vol. 185, no. 2, pp. 741–748, 1991. View at Publisher · View at Google Scholar · View at Scopus
  51. J. K. Fazakerley, “Semliki forest virus infection of laboratory mice: a model to study the pathogenesis of viral encephalitis,” Archives of Virology, no. 18, supplement, pp. 179–190, 2004. View at Google Scholar · View at Scopus
  52. G. J. Atkins, B. J. Sheahan, and P. Liljeström, “The molecular pathogenesis of Semliki Forest virus: a model virus made useful?” Journal of General Virology, vol. 80, no. 9, pp. 2287–2297, 1999. View at Google Scholar · View at Scopus
  53. G. J. Atkins, B. J. Sheahan, and N. J. Dimmock, “Semliki Forest virus infection of mice: a model for genetic and molecular analysis of viral pathogenicity,” Journal of General Virology, vol. 66, pp. 395–408, 1985. View at Google Scholar · View at Scopus
  54. G. J. Atkins, M. J. E. M. F. Mabruk, G. M. Glasgow, A. M. Griffin, and B. J. Sheahan, “Mechanisms of viral teratogenesis,” Reviews in Medical Virology, vol. 5, no. 2, pp. 75–86, 1995. View at Publisher · View at Google Scholar · View at Scopus
  55. B. J. Sheahan, M. C. Gates, J. F. Caffrey, and G. J. Atkins, “Oligodendrocyte infection and demyelination produced in mice by the M9 mutant of semliki forest virus,” Acta Neuropathologica, vol. 60, no. 3-4, pp. 257–265, 1983. View at Google Scholar · View at Scopus
  56. P. N. Barrett, B. J. Sheahan, and G. J. Atkins, “Isolation and preliminary characterization of Semliki Forest virus mutants with altered virulence,” Journal of General Virology, vol. 49, no. 1, pp. 141–147, 1980. View at Google Scholar · View at Scopus
  57. G. J. Atkins and B. J. Sheahan, “Semliki forest virus neurovirulence mutants have altered cytopathogenesis for central nervous system cells,” Infection and Immunity, vol. 36, no. 1, pp. 333–341, 1982. View at Google Scholar · View at Scopus
  58. G. J. Atkins, “The avirulent A7 strain of Semliki Forest virus has reduced cytopathogenicity for neuroblastoma cells compared to the virulent L10 strain,” Journal of General Virology, vol. 64, no. 6, pp. 1401–1404, 1983. View at Google Scholar · View at Scopus
  59. J. K. Fazakerley, “Pathogenesis of Semliki Forest virus encephalitis,” Journal of NeuroVirology, vol. 8, no. 2, supplement, pp. 66–74, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. B. J. Sheahan, M. A. Ibrahim, and G. J. Atkins, “Demyelination of olfactory pathways in mice following intranasal infection with the avirulent A7 strain of Semliki Forest virus,” European Journal of Veterinary Pathology, vol. 2, pp. 117–125, 1996. View at Google Scholar
  61. D. J. Sammin, D. Butler, G. J. Atkins, and B. J. Sheahan, “Cell death mechanisms in the olfactory bulb of rats infected intranasally with Semliki Forest virus,” Neuropathology and Applied Neurobiology, vol. 25, no. 3, pp. 236–243, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Liljestrom, S. Lusa, D. Huylebroeck, and H. Garoff, “In vitro mutagenesis of a full-length cDNA clone of semliki forest virus: the small 6,000-molecular-weight membrane protein modulates virus release,” Journal of Virology, vol. 65, no. 8, pp. 4107–4113, 1991. View at Google Scholar · View at Scopus
  63. G. M. Glasgow, H. M. Killen, P. Liljestrom, B. J. Sheahan, and G. J. Atkins, “A single amino acid change in the E2 spike protein of a virulent strain of Semliki Forest virus attenuates pathogenicity,” Journal of General Virology, vol. 75, no. 3, pp. 663–668, 1994. View at Google Scholar · View at Scopus
  64. M. G. Santagati, J. A. Määttä, M. Röyttä, A. A. Salmi, and A. E. Hinkkanen, “The significance of the 3'-nontranslated region and E2 amino acid mutations in the virulence of Semliki Forest virus in mice,” Virology, vol. 243, no. 1, pp. 66–77, 1998. View at Publisher · View at Google Scholar · View at Scopus
  65. M. G. Santagati, J. A. Maatta, P. V. Itaranta, A. A. Salmi, and A. E. Hinkkanen, “The Semliki Forest virus E2 gene as a virulence determinant,” Journal of General Virology, vol. 76, no. 1, pp. 47–52, 1995. View at Google Scholar · View at Scopus
  66. C. J. Tarbatt, G. M. Glasgow, D. A. Mooney, B. J. Sheahan, and G. J. Atkins, “Sequence analysis of the avirulent, demyelinating A7 strain of Semliki Forest virus,” Journal of General Virology, vol. 78, no. 7, pp. 1551–1557, 1997. View at Google Scholar · View at Scopus
  67. M. T. Tuittila, M. G. Santagati, M. Röyttä, J. A. Määttä, and A. E. Hinkkanen, “Replicase complex genes of Semliki Forest virus confer lethal neurovirulence,” Journal of Virology, vol. 74, no. 10, pp. 4579–4589, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Tuittila and A. E. Hinkkanen, “Amino acid mutations in the replicase protein nsP3 of Semliki Forest virus cumulatively affect neurovirulence,” Journal of General Virology, vol. 84, no. 6, pp. 1525–1533, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. C. H. Logue, B. J. Sheahan, and G. J. Atkins, “The 5 untranslated region as a pathogenicity determinant of Semliki Forest virus in mice,” Virus Genes, vol. 36, no. 2, pp. 313–321, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. S. E. Galbraith, B. J. Sheahan, and G. J. Atkins, “Deletions in the hypervariable domain of the nsP3 gene attenuate Semliki Forest virus virulence,” Journal of General Virology, vol. 87, no. 4, pp. 937–947, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. S. A. Deuber and J. Pavlovic, “Virulence of a mouse-adapted Semliki Forest virus strain is associated with reduced susceptibility to interferon,” Journal of General Virology, vol. 88, no. 7, pp. 1952–1959, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. I. M. Balluz, G. M. Glasgow, H. M. Killen, M. J. M. E. F. Mabruk, B. J. Sheahan, and G. J. Atkins, “Virulent and avirulent strains of Semliki Forest virus show similar cell tropism for the murine central nervous system but differ in the severity and rate of induction of cytolytic damage,” Neuropathology and Applied Neurobiology, vol. 19, no. 3, pp. 233–239, 1993. View at Google Scholar · View at Scopus
  73. J. K. Fazakerley, S. Pathak, M. Scallan, S. Amor, and H. Dyson, “Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons,” Virology, vol. 195, no. 2, pp. 627–637, 1993. View at Publisher · View at Google Scholar · View at Scopus
  74. J. K. Fazakerley and H. E. Webb, “Semliki Forest virus-induced, immune-mediated demyelination: adoptive transfer studies and viral persistence in nude mice,” Journal of General Virology, vol. 68, no. 2, pp. 377–385, 1987. View at Google Scholar · View at Scopus
  75. I. Subak-Sharpe, H. Dyson, and J. Fazakerley, “In vivo depletion of CD8+ T cells prevents lesions of demyelination in Semliki Forest virus infection,” Journal of Virology, vol. 67, no. 12, pp. 7629–7633, 1993. View at Google Scholar · View at Scopus
  76. R. Fragkoudis, C. M. Ballany, A. Boyd, and J. K. Fazakerley, “In Semliki Forest virus encephalitis, antibody rapidly clears infectious virus and is required to eliminate viral material from the brain, but is not required to generate lesions of demyelination,” Journal of General Virology, vol. 89, no. 10, pp. 2565–2568, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. T. A. Smith-Norowitz, R. A. Sobel, and F. Mokhtarian, “B cells and antibodies in the pathogenesis of myelin injury in Semliki Forest Virus encephalomyelitis,” Cellular Immunology, vol. 200, no. 1, pp. 27–35, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. F. Mokhtarian, C. M. Huan, C. Roman, and C. S. Raine, “Semliki Forest virus-induced demyelination and remyelination - Involvement of B cells and anti-myelin antibodies,” Journal of Neuroimmunology, vol. 137, no. 1-2, pp. 19–31, 2003. View at Publisher · View at Google Scholar · View at Scopus
  79. F. Mokhtarian, Z. Zhang, Y. Shi, E. Gonzales, and R. A. Sobel, “Molecular mimicry between a viral peptide and a myelin oligodendrocyte glycoprotein peptide induces autoimmune demyelinating disease in mice,” Journal of Neuroimmunology, vol. 95, no. 1-2, pp. 43–54, 1999. View at Publisher · View at Google Scholar · View at Scopus
  80. M. C. Gates, B. J. Sheahan, M. A. O'Sullivan, and G. J. Atkins, “The pathogenecity of the A7, M9 and L10 strains of semliki forest virus for weanling mice and primary mouse brain cell cultures,” Journal of General Virology, vol. 66, no. 11, pp. 2365–2373, 1985. View at Google Scholar · View at Scopus
  81. G. J. Atkins, B. J. Sheahan, and D. A. Mooney, “Pathogenicity of Semliki Forest virus for the rat central nervous system and primary rat neural cell cultures: possible implications for the pathogenesis of multiple sclerosis,” Neuropathology and Applied Neurobiology, vol. 16, no. 1, pp. 57–68, 1990. View at Google Scholar · View at Scopus
  82. R. Fragkoudis, N. Tamberg, R. Siu et al., “Neurons and oligodendrocytes in the mouse brain differ in their ability to replicate Semliki Forest virus,” Journal of NeuroVirology, vol. 15, no. 1, pp. 57–70, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. J. M. B. Smyth, B. J. Sheahan, and G. J. Atkins, “Multiplication of virulent and demyelinating Semliki Forest virus in the mouse central nervous systemml: consequences in BALB/c and SJL mice,” Journal of General Virology, vol. 71, no. 11, pp. 2575–2583, 1990. View at Google Scholar · View at Scopus
  84. S. M. Donnelly, B. J. Sheahan, and G. J. Atkins, “Long-term effects of Semliki Forest virus infection in the mouse central nervous system,” Neuropathology and Applied Neurobiology, vol. 23, no. 3, pp. 235–241, 1997. View at Google Scholar · View at Scopus
  85. F. Safavi, J. P. Feliberti, C. S. Raine, and F. Mokhtarian, “Role of γδ T cells in antibody production and recovery from SFV demyelinating disease,” Journal of Neuroimmunology, vol. 235, no. 1-2, pp. 18–26, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. K. Lundstrom, W. Pralong, and J. C. Martinou, “Anti-apoptotic effect of Bcl-2 overexpression in RIN cells infected with Semliki Forest virus,” Apoptosis, vol. 2, no. 2, pp. 189–191, 1997. View at Google Scholar · View at Scopus
  87. M. F. Scallan, T. E. Allsopp, and J. K. Fazakerley, “bcl-2 Acts early to restrict semliki forest virus replication and delays virus-induced programmed cell death,” Journal of Virology, vol. 71, no. 2, pp. 1583–1590, 1997. View at Google Scholar · View at Scopus
  88. A. M. Murphy, B. J. Sheahan, and G. J. Atkins, “Induction of apoptosis in Bcl-2-expressing rat prostate cancer cells using the Semliki Forest virus vector,” International Journal of Cancer, vol. 94, no. 4, pp. 572–578, 2001. View at Publisher · View at Google Scholar · View at Scopus
  89. D. Grandgirard, E. Studer, L. Monney et al., “Alphaviruses induce apoptosis in Bcl-2-overexpressing cells: evidence for a caspase-mediated, proteolytic inactivation of Bcl-2,” EMBO Journal, vol. 17, no. 5, pp. 1268–1278, 1998. View at Publisher · View at Google Scholar · View at Scopus
  90. R. Fragkoudis, Y. Chi, R. W. C. Siu et al., “Semliki Forest virus strongly reduces mosquito host defence signaling,” Insect Molecular Biology, vol. 17, no. 6, pp. 647–656, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. G. Attarzadeh-Yazdi, R. Fragkoudis, Y. Chi et al., “Cell-to-cell spread of the RNA interference response suppresses semliki forest virus (SFV) infection of mosquito cell cultures and cannot be antagonized by SFV,” Journal of Virology, vol. 83, no. 11, pp. 5735–5748, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. R. W. C. Siu, R. Fragkoudis, P. Simmonds et al., “Antiviral RNA interference responses induced by Semliki Forest virus infection of mosquito cells: characterization, origin, and frequency-dependent functions of virus-derived small interfering RNAs,” Journal of Virology, vol. 85, no. 6, pp. 2907–2917, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. G. J. Atkins, J. Carter, and B. J. Sheahan, “Effect of alphavirus infection on mouse embryos,” Infection and Immunity, vol. 38, no. 3, pp. 1285–1290, 1982. View at Google Scholar · View at Scopus
  94. A. R. Milner and I. D. Marshall, “Pathogenesis of in utero infections with abortogenic and non-abortogenic alphaviruses in mice,” Journal of Virology, vol. 50, no. 1, pp. 66–72, 1984. View at Google Scholar · View at Scopus
  95. A. R. Milner, I. D. Marshall, and A. Mullbacher, “Effect of pregnancy on stimulation of alphavirus immunity in mice,” Journal of Virology, vol. 50, no. 1, pp. 73–76, 1984. View at Google Scholar · View at Scopus
  96. A. M. Hearne, M. A. O'Sullivan, and G. J. Atkins, “Infection of cultured early mouse embryos with Semliki Forest and rubella viruses,” Journal of General Virology, vol. 67, no. 6, pp. 1091–1098, 1986. View at Google Scholar · View at Scopus
  97. A. M. Hearne, M. A. O'Sullivan, and G. J. Atkins, “Isolation and preliminary characterization of Semliki Forest virus mutants with altered pathogenicity for mouse embryos,” Journal of General Virology, vol. 68, no. 1, pp. 107–113, 1987. View at Google Scholar · View at Scopus
  98. M. J. E. M. F. Mabruk, A. M. Flack, G. M. Glasgow et al., “Teratogenicity of the Semliki Forest virus mutant ts22 for the foetal mouse: induction of skeletal and skin defects,” Journal of General Virology, vol. 69, no. 11, pp. 2755–2762, 1988. View at Google Scholar · View at Scopus
  99. M. J. E. M. F. Mabruk, G. M. Glasgow, A. M. Flack et al., “Effect of infection with the ts22 mutant of Semliki Forest virus on development of the central nervous system in the fetal mouse,” Journal of Virology, vol. 63, no. 9, pp. 4027–4033, 1989. View at Google Scholar · View at Scopus
  100. http://emedicine.medscape.com/article/233913.
  101. S. C. Weaver and W. K. Reisen, “Present and future arboviral threats,” Antiviral Research, vol. 85, no. 2, pp. 328–345, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. M. A. Zacks and S. Paessler, “Encephalitic alphaviruses,” Veterinary Microbiology, vol. 140, no. 3-4, pp. 281–286, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. S. C. Weaver, C. Ferro, R. Barrera, J. Boshell, and J. C. Navarro, “Venezuelan equine encephalitis,” Annual Review of Entomology, vol. 49, pp. 141–174, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. G. H. MacDonald and R. E. Johnston, “Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis,” Journal of Virology, vol. 74, no. 2, pp. 914–922, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. P. C. Charles, E. Walters, F. Margolis, and R. E. Johnston, “Mechanism of neuroinvasion of Venezuelan equine encephalitis virus in the mouse,” Virology, vol. 208, no. 2, pp. 662–671, 1995. View at Publisher · View at Google Scholar · View at Scopus
  106. A. Schäfer, C. B. Brooke, A. C. Whitmore, and R. E. Johnston, “The role of the blood-brain barrier during Venezuelan equine encephalitis virus infection,” Journal of Virology, vol. 85, pp. 10682–10690, 2011. View at Google Scholar
  107. A. C. Jackson and J. P. Rossiter, “Apoptotic cell death is an important cause of neuronal injury in experimental Venezuelan equine encephalitis virus infection of mice,” Acta Neuropathologica, vol. 93, no. 4, pp. 349–353, 1997. View at Publisher · View at Google Scholar · View at Scopus
  108. A. Sharma and R. K. Maheshwari, “Oligonucleotide array analysis of Toll-like receptors and associated signalling genes in Venezuelan equine encephalitis virus-infected mouse brain,” Journal of General Virology, vol. 90, no. 8, pp. 1836–1847, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. J. D. Simmons, L. J. White, T. E. Morrison et al., “Venezuelan equine encephalitis virus disrupts STAT1 signaling by distinct mechanisms independent of host shutoff,” Journal of Virology, vol. 83, no. 20, pp. 10571–10581, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Schäfer, A. C. Whitmore, J. L. Konopka, and R. E. Johnston, “Replicon particles of Venezuelan equine encephalitis virus as a reductionist murine model for encephalitis,” Journal of Virology, vol. 83, no. 9, pp. 4275–4286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. B. J. B. Johnson, R. M. Kinney, C. L. Kost, and D. W. Trent, “Molecular determinants of alphavirus neurovirulence: nucleotide and deduced protein sequence changes during attenuation of Venezuelan equine encephalitis virus,” Journal of General Virology, vol. 67, no. 9, pp. 1951–1960, 1986. View at Google Scholar · View at Scopus
  112. N. L. Davis, L. V. Willis, J. F. Smith, and R. E. Johnston, “In vitro synthesis of infectious Venezuelan equine encephalitis virus RNA from a cDNA clone: analysis of a viable deletion mutant,” Virology, vol. 171, no. 1, pp. 189–204, 1989. View at Google Scholar · View at Scopus
  113. N. L. Davis, N. Powell, G. F. Greenwald et al., “Attenuating mutations in the E2 glycoprotein gene of Venezuelan equine encephalitis virus: construction of single and multiple mutants in a full-length cDNA clone,” Virology, vol. 183, no. 1, pp. 20–31, 1991. View at Publisher · View at Google Scholar · View at Scopus
  114. N. L. Davis, F. B. Grieder, J. F. Smith et al., “A molecular genetic approach to the study of Venezuelan equine encephalitis virus pathogenesis,” Archives of Virology, vol. 9, pp. 99–109, 1994. View at Google Scholar · View at Scopus
  115. J. F. Aronson, F. B. Grieder, N. L. Davis et al., “A single-site mutant and revertants arising in vivo define early steps in the pathogenesis of venezuelan equine encephalitis virus,” Virology, vol. 270, no. 1, pp. 111–123, 2000. View at Publisher · View at Google Scholar · View at Scopus
  116. L. J. White, J. G. Wang, N. L. Davis, and R. E. Johnston, “Role of alpha/beta interferon in Venezuelan equine encephalitisb1 virus pathogenesis: effect of an attenuating mutation in the 5 untranslated region,” Journal of Virology, vol. 75, no. 8, pp. 3706–3718, 2001. View at Publisher · View at Google Scholar · View at Scopus
  117. A. C. Brault, A. M. Powers, E. C. Holmes, C. H. Woelk, and S. C. Weaver, “Positively charged amino acid substitutions in the E2 envelope glycoprotein are associated with the emergence of Venezuelan equine encephalitis virus,” Journal of Virology, vol. 76, no. 4, pp. 1718–1730, 2002. View at Publisher · View at Google Scholar · View at Scopus
  118. A. C. Brault, A. M. Powers, and S. C. Weaver, “Vector infection determinants of Venezuelan equine encephalitis virus reside within the E2 envelope glycoprotein,” Journal of Virology, vol. 76, no. 12, pp. 6387–6392, 2002. View at Publisher · View at Google Scholar · View at Scopus
  119. S. C. Weaver, M. Anishchenko, R. Bowen et al., “Genetic determinants of Venezuelan equine encephalitis emergence,” Archives of Virology, no. 18, pp. 43–64, 2004. View at Google Scholar · View at Scopus
  120. A. C. Brault, A. M. Powers, D. Ortiz, J. G. Estrada-Franco, R. Navarro-Lopez, and S. C. Weaver, “Venezuelan equine encephalitis emergence: enhanced vector infection from a single amino acid substitution in the envelope glycoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 31, pp. 11344–11349, 2004. View at Publisher · View at Google Scholar · View at Scopus
  121. I. P. Greene, S. Paessler, M. Anishchenko et al., “Venezuelan equine encephalitis virus in the guinea pig model: evidence for epizootic virulence determinants outside the E2 envelope glycoprotein gene,” American Journal of Tropical Medicine and Hygiene, vol. 72, no. 3, pp. 330–338, 2005. View at Google Scholar · View at Scopus
  122. F. Del Piero, P. A. Wilkins, E. J. Dubovi, B. Biolatti, and C. Cantile, “Clinical, pathologic, immunohistochemical, and virologic findings of eastern equine encephalomyelitis in two horses,” Veterinary Pathology, vol. 38, no. 4, pp. 451–456, 2001. View at Publisher · View at Google Scholar · View at Scopus
  123. S. M. Williams, R. M. Fulton, J. S. Patterson, and W. M. Reed, “Diagnosis of Eastern equine encephalitis by immunohistochemistry in two flocks of Michigan ring-neck pheasants,” Avian Diseases, vol. 44, no. 4, pp. 1012–1016, 2000. View at Google Scholar · View at Scopus
  124. A. C. Brault, A. M. Powers, C. L. Villarreal Chavez et al., “Genetic and antigenic diversity among eastern equine encephalitis viruses from North, Central, and South America,” American Journal of Tropical Medicine and Hygiene, vol. 61, no. 4, pp. 579–586, 1999. View at Google Scholar · View at Scopus
  125. http://emedicine.medscape.com/article/233442.
  126. S. Paessler, P. Aguilar, M. Anishchenko et al., “The hamster as an animal model for eastern equine encephalitis- and its use in studies of virus entrance into the brain,” Journal of Infectious Diseases, vol. 189, no. 11, pp. 2072–2076, 2004. View at Publisher · View at Google Scholar · View at Scopus
  127. A. P. Adams, J. F. Aronson, S. D. Tardif et al., “Common marmosets (Callithrix jacchus) as a nonhuman primate model to assess the virulence of eastern equine encephalitis virus strains,” Journal of Virology, vol. 82, no. 18, pp. 9035–9042, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. P. V. Aguilar, S. Paessler, A. S. Carrara et al., “Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus,” Journal of Virology, vol. 79, no. 17, pp. 11300–11310, 2005. View at Publisher · View at Google Scholar · View at Scopus
  129. P. V. Aguilar, A. P. Adams, E. Wang et al., “Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence,” Journal of Virology, vol. 82, no. 10, pp. 4920–4930, 2008. View at Publisher · View at Google Scholar · View at Scopus
  130. C. L. Gardner, J. Yin, C. W. Burke, W. B. Klimstra, and K. D. Ryman, “Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice,” Virology, vol. 390, no. 2, pp. 338–347, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. C. L. Gardner, C. W. Burke, M. Z. Tesfay, P. J. Glass, W. B. Klimstra, and K. D. Ryman, “Eastern and Venezuelan equine encephalitis viruses differ in their ability to infect dendritic cells and macrophages: impact of altered cell tropism on pathogenesis,” Journal of Virology, vol. 82, no. 21, pp. 10634–10646, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. N. L. Forrester, J. L. Kenney, E. Deardorff, E. Wang, and S. C. Weaver, “Western equine encephalitis submergence: lack of evidence for a decline in virus virulence,” Virology, vol. 380, no. 2, pp. 170–172, 2008. View at Publisher · View at Google Scholar · View at Scopus
  133. http://emedicine.medscape.com/article/233568.
  134. C. S. Hahn, S. Lustig, E. G. Strauss, and J. H. Strauss, “Western equine encephalitis virus is a recombinant virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 16, pp. 5997–6001, 1988. View at Google Scholar · View at Scopus
  135. S. C. Weaver, A. Hagenbaugh, L. A. Bellew et al., “A comparison of the nucleotide sequences of eastern and western equine encephalomyelitis viruses with those of other alphaviruses and related RNA viruses,” Virology, vol. 197, pp. 375–390, 1993. View at Google Scholar
  136. S. C. Weaver, W. Kang, Y. Shirako, T. Rümenapf, E. G. Strauss, and J. H. Strauss, “Recombinational history and molecular evolution of western equine encephalomyelitis complex alphaviruses,” Journal of Virology, vol. 71, no. 1, pp. 613–623, 1997. View at Google Scholar · View at Scopus
  137. D. J. Netolitzky, F. L. Schmaltz, M. D. Parker et al., “Complete genomic RNA sequence of western equine encephalitis virus and expression of the structural genes,” Journal of General Virology, vol. 81, no. 1, pp. 151–159, 2000. View at Google Scholar · View at Scopus
  138. J. G. Julander, V. Siddharthan, L. M. Blatt, K. Schafer, R. W. Sidwell, and J. D. Morrey, “Effect of exogenous interferon and an interferon inducer on western equine encephalitis virus disease in a hamster model,” Virology, vol. 360, no. 2, pp. 454–460, 2007. View at Publisher · View at Google Scholar · View at Scopus
  139. T. I. Bianchi, G. Aviles, T. P. Monath, and M. S. Sabattini, “Western equine encephalomyelitis: virulence markers and their epidemiologic significance,” American Journal of Tropical Medicine and Hygiene, vol. 49, no. 3, pp. 322–328, 1993. View at Google Scholar · View at Scopus
  140. L. P. Nagata, W. G. Hu, M. Parker et al., “Infectivity variation and genetic diversity among strains of Western equine encephalitis virus,” Journal of General Virology, vol. 87, no. 8, pp. 2353–2361, 2006. View at Publisher · View at Google Scholar · View at Scopus
  141. C. H. Logue, C. F. Bosio, T. Welte et al., “Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model,” Journal of General Virology, vol. 90, no. 8, pp. 1848–1858, 2009. View at Publisher · View at Google Scholar · View at Scopus
  142. K. M. Castorena, D. C. Peltier, W. Peng, and D. J. Miller, “Maturation-dependent responses of human neuronal cells to western equine encephalitis virus infection and type I interferons,” Virology, vol. 372, no. 1, pp. 208–220, 2008. View at Publisher · View at Google Scholar · View at Scopus
  143. http://www.patient.co.uk/doctor/Ross-River-Virus-Infection.htm.
  144. M. La Linn, J. A. Eble, C. Lübken et al., “An arthritogenic alphavirus uses the α1β1 integrin collagen receptor,” Virology, vol. 336, no. 2, pp. 229–239, 2005. View at Publisher · View at Google Scholar · View at Scopus
  145. S. U. Vrati, P. J. Kerr, R. C. Weir, and L. Dalgarno, “Entry kinetics and mouse virulence of Ross River virus mutants altered in neutralization epitopes,” Journal of Virology, vol. 70, no. 3, pp. 1745–1750, 1996. View at Google Scholar · View at Scopus
  146. R. S. Shabman, T. E. Morrison, C. Moore et al., “Differential induction of type I interferon responses in myeloid dendritic cells by mosquito and mammalian-cell-derived alphaviruses,” Journal of Virology, vol. 81, no. 1, pp. 237–247, 2007. View at Publisher · View at Google Scholar · View at Scopus
  147. T. E. Morrison, R. J. Fraser, P. N. Smith, S. Mahalingam, and M. T. Heise, “Complement contributes to inflammatory tissue destruction in a mouse model of ross river virus-induced disease,” Journal of Virology, vol. 81, no. 10, pp. 5132–5143, 2007. View at Publisher · View at Google Scholar · View at Scopus
  148. T. E. Morrison, J. D. Simmons, and M. T. Heise, “Complement receptor 3 promotes severe Ross River virus-induced disease,” Journal of Virology, vol. 82, no. 22, pp. 11263–11272, 2008. View at Publisher · View at Google Scholar · View at Scopus
  149. B. M. Gunn, T. E. Morrison, and A. C. Whitmore, “Mannose binding lectin is required for alphavirus-induced arthritis/myositis,” PLOS Pathogens, vol. 8, no. 3, Article ID e1002586, 2012. View at Google Scholar
  150. L. J. Herrero, M. Nelson, A. Srikiatkhachorn et al., “Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 29, pp. 12048–12053, 2011. View at Publisher · View at Google Scholar · View at Scopus
  151. L. M. Neighbours, K. Long, A. C. Whitmore, and M. T. Heise, “Myd88-dependent toll-like receptor 7 signaling mediates protection from severe Ross River virus-induced disease in mice,” Journal of Virology, vol. 86, no. 19, pp. 10675–10685, 2012. View at Google Scholar
  152. H. J. Jupille, L. Oko, K. A. Stoermer et al., “Mutations in nsP1 and PE2 are critical determinants of Ross River virus-induced musculoskeletal inflammatory disease in a mouse model,” Virology, vol. 410, no. 1, pp. 216–227, 2011. View at Publisher · View at Google Scholar · View at Scopus
  153. http://www.who.int/mediacentre/factsheets/fs327/en/.
  154. O. Schwartz and M. L. Albert, “Biology and pathogenesis of chikungunya virus,” Nature Reviews Microbiology, vol. 8, no. 7, pp. 491–500, 2010. View at Publisher · View at Google Scholar · View at Scopus
  155. I. Schuffenecker, I. Iteman, A. Michault et al., “Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak,” PLoS Medicine, vol. 3, no. 7, pp. 1058–1070, 2006. View at Publisher · View at Google Scholar · View at Scopus
  156. K. A. Tsetsarkin, C. E. McGee, S. M. Volk, D. L. Vanlandingham, S. C. Weaver, and S. Higgs, “Epistatic roles of E2 glycoprotein mutations in adaption of Chikungunya virus to Aedes albopictus and Ae. Aegypti mosquitoes,” PLoS ONE, vol. 4, no. 8, Article ID e6835, 2009. View at Publisher · View at Google Scholar · View at Scopus
  157. K. A. Tsetsarkin and S. C. Weaver, “Sequential adaptive mutations enhance efficient vector switching by Chikungunya virus and its epidemic emergence,” PLOS Pathogens, vol. 7, Article ID e1002412, 2011. View at Google Scholar
  158. S. Thangamani, S. Higgs, S. Ziegler, D. Vanlandingham, R. Tesh, and S. Wikel, “Host immune response to mosquito-transmitted chikungunya virus differs from that elicited by needle inoculated virus,” PLoS ONE, vol. 5, no. 8, Article ID e12137, 2010. View at Publisher · View at Google Scholar · View at Scopus
  159. N. Wauquier, P. Becquart, D. Nkoghe, C. Padilla, A. Ndjoyi-Mbiguino, and E. M. Leroy, “The acute phase of Chikungunya virus infection in humans is associated with strong innate immunity and T CD8 cell activation,” Journal of Infectious Diseases, vol. 204, no. 1, pp. 115–123, 2011. View at Publisher · View at Google Scholar · View at Scopus
  160. C. Schilte, T. Couderc, F. Chretien et al., “Type I IFN controls chikungunya virus via its action on nonhematopoietic cells,” Journal of Experimental Medicine, vol. 207, no. 2, pp. 429–442, 2010. View at Publisher · View at Google Scholar · View at Scopus
  161. Z. Her, B. Malleret, M. Chan et al., “Active infection of human blood monocytes by Chikungunya virus triggers an innate immune response,” Journal of Immunology, vol. 184, no. 10, pp. 5903–5913, 2010. View at Publisher · View at Google Scholar · View at Scopus
  162. K. Labadie, T. Larcher, C. Joubert et al., “Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages,” Journal of Clinical Investigation, vol. 120, no. 3, pp. 894–906, 2010. View at Publisher · View at Google Scholar · View at Scopus
  163. C. L. Gardner, C. W. Burke, S. T. Higgs, W. B. Klimstra, and K. D. Ryman, “Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate,” Virology, vol. 425, pp. 103–112, 2012. View at Google Scholar
  164. J. J. Fros, W. J. Liu, N. A. Prow et al., “Chikungunya virus nonstructural protein 2 inhibits type I/II interferon-stimulated JAK-STAT signaling,” Journal of Virology, vol. 84, no. 20, pp. 10877–10887, 2010. View at Publisher · View at Google Scholar · View at Scopus
  165. http://www.allmosquitos.com/mosquito-diseases/mosquito-transmitted-human-diseases/o039nyong039nyong-fever.htm.
  166. C. Sim, Y. S. Hong, K. A. Tsetsarkin, D. L. Vanlandingham, S. Higgs, and F. H. Collins, “Anopheles gambiae heat shock protein cognate 70B impedes o'nyong-nyong virus replication,” BMC Genomics, vol. 8, article 231, 2007. View at Publisher · View at Google Scholar · View at Scopus
  167. K. M. Keene, B. D. Foy, I. Sanchez-Vargas, B. J. Beaty, C. D. Blair, and K. E. Olson, “RNA interference acts as a natural antiviral response to O'nyong-nyong virus (Alphavirus; Togaviridae) infection of Anopheles gambiae,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 49, pp. 17240–17245, 2004. View at Publisher · View at Google Scholar · View at Scopus
  168. D. L. Vanlandingham, K. Tsetsarkin, K. A. Klingler et al., “Determinants of vector specificity of o'nyong nyong and chikungunya viruses in Anopheles and Aedes mosquitoes,” American Journal of Tropical Medicine and Hygiene, vol. 74, no. 4, pp. 663–669, 2006. View at Google Scholar · View at Scopus
  169. C. Sim, Y. S. Hong, D. L. Vanlandingham et al., “Modulation of Anopheles gambiae gene expression in response to o'nyong-nyong virus infection,” Insect Molecular Biology, vol. 14, no. 5, pp. 475–481, 2005. View at Publisher · View at Google Scholar · View at Scopus
  170. K. M. Myles, C. L. H. Kelly, J. P. Ledermann, and A. M. Powers, “Effects of an opal termination codon preceding the nsP4 gene sequence in the O'nyong-nyong virus genome on Anopheles gambiae infectivity,” Journal of Virology, vol. 80, no. 10, pp. 4992–4997, 2006. View at Publisher · View at Google Scholar · View at Scopus
  171. M. F. McLoughlin and D. A. Graham, “Alphavirus infections in salmonids—a review,” Journal of Fish Diseases, vol. 30, no. 9, pp. 511–531, 2007. View at Publisher · View at Google Scholar · View at Scopus
  172. J. H. Weston, M. D. Welsh, M. F. McLoughlin, and D. Todd, “Salmon pancreas disease virus, an alphavirus infecting farmed Atlantic salmon, Salmo salar L,” Virology, vol. 256, no. 2, pp. 188–195, 1999. View at Publisher · View at Google Scholar · View at Scopus
  173. D. A. Graham, H. L. Jewhurst, M. F. McLoughlin et al., “Serological, virological and histopathological study of an outbreak of sleeping disease in farmed rainbow trout Oncorhynchus mykiss,” Diseases of Aquatic Organisms, vol. 74, no. 3, pp. 191–197, 2007. View at Google Scholar · View at Scopus
  174. D. A. Graham, H. Jewhurst, M. F. McLoughlin et al., “Sub-clinical infection of farmed Atlantic salmon Salmo salar with salmonid alphavirus—a prospective longitudinal study,” Diseases of Aquatic Organisms, vol. 72, no. 3, pp. 193–199, 2006. View at Google Scholar · View at Scopus
  175. C. Xu, T. C. Guo, S. Mutoloki, Ø. Haugland, I. S. Marjara, and Ø. Evensen, “Alpha interferon and not gamma interferon inhibits salmonid alphavirus subtype 3 replication in vitro,” Journal of Virology, vol. 84, no. 17, pp. 8903–8912, 2010. View at Publisher · View at Google Scholar · View at Scopus
  176. T. K. Herath, J. E. Bron, K. D. Thompson et al., “Transcriptomic analysis of the host response to early stage salmonid alphavirus (SAV-1) infection in Atlantic salmon Salmosalar L,” Fish and Shellfish Immunology, vol. 32, pp. 796–807, 2012. View at Google Scholar