1887

Abstract

Alphaviruses are enveloped viruses with a positive-stranded RNA genome, of the family . In mammals and birds they are mosquito-transmitted and are of veterinary and medical importance. They cause primarily two types of disease: encephalitis and polyarthritis. Here we review attempts to understand the molecular basis of encephalitis and virulence for the central nervous system (CNS) in mouse models. Sindbis virus (SINV) was the first virus to be studied in this way. Other viruses analysed are Semliki Forest virus (SFV), Venezuelan equine encephalitis virus, Eastern equine encephalitis virus and Western equine encephalitis virus. Neurovirulence was found to be associated with damage to neurons in the CNS. It mapped mainly to the E2 region of the genome, and to the nsP3 gene. Also, avirulent natural isolates of both SINV and SFV have been found to have more rapid cleavage of nonstructural proteins due to mutations in the nsP1–nsP2 cleavage site. Immune-mediated demyelination for avirulent SFV has been shown to be associated with infection of oligodendrocytes. For Chikungunya virus, an emerging alphavirus that uncommonly causes encephalitis, analysis of the molecular basis of CNS pathogenicity is beginning. Experiments on SINV and SFV have indicated that virulence may be related to the resistance of virulent virus to interferon action. Although the E2 protein may be involved in tropism for neurons and passage across the blood-brain barrier, the role of the nsP3 protein during infection of neurons is unknown. More information in these areas may help to further explain the neurovirulence of alphaviruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000467
2016-06-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/6/1283.html?itemId=/content/journal/jgv/10.1099/jgv.0.000467&mimeType=html&fmt=ahah

References

  1. Aguilar P. V., Adams A. P., Wang E., Kang W., Carrara A.-S., Anishchenko M., Frolov I., Weaver S. C. 2008a; Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence. J Virol 82:4920–4930 [View Article]
    [Google Scholar]
  2. Aguilar P. V., Leung L. W., Wang E., Weaver S. C., Basler C. F. 2008b; A five-amino-acid deletion of the eastern equine encephalitis virus capsid protein attenuates replication in mammalian systems but not in mosquito cells. J Virol 82:6972–6983 [View Article]
    [Google Scholar]
  3. Ahola T., Courderc T., Ng L. F., Hallengärd D., Powers A., Lecuit M., Esteban M., Merits A., Roques P., Liljestrom P. 2015; Therapeutics and vaccines against chikungunya virus. Vector Born Zoonotic Dis 15:250–257 [View Article][PubMed]
    [Google Scholar]
  4. Aronson J. F., Grieder F. B., Davis N. L., Charles P. C., Knott T., Brown K., Johnston R. E. 2000; A single-site mutant and revertants arising in vivo define early steps in the pathogenesis of Venezuelan Equine Encephalitis virus. Virology 270:111–123 [View Article]
    [Google Scholar]
  5. Arpino C., Curatolo P., Rezza G. 2009; Chikungunya and the nervous system: What we do and do not know. Rev Med Virol 19:121–129 [View Article][PubMed]
    [Google Scholar]
  6. Atkins G. J. 1983; The avirulent A7 strain of Semliki Forest virus has reduced cytopathogenicity for neuroblastoma cells compared to the virulent L10 strain. J Gen Virol 64:1401–1404 [View Article][PubMed]
    [Google Scholar]
  7. Atkins G. J., Sheahan B. J. 1982; Semliki Forest virus neurovirulence mutants have altered cytopathogenicity for central nervous system cells. Infect Immun 36:333–341[PubMed]
    [Google Scholar]
  8. Atkins G. J., Sheahan B. J., Dimmock N. J. 1985; Semliki Forest virus infection of mice: A model for genetic and molecular analysis of viral pathogenicity. J Gen Virol 66:395–408 [View Article][PubMed]
    [Google Scholar]
  9. Atkins G. J., Sheahan B. J., Mooney D. A. 1990; 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. Neuropathol Appl Neurobiol 16:57–68 [View Article][PubMed]
    [Google Scholar]
  10. Atkins G. J., Mabruk M. J. E. M. F., Glasgow G. M., Griffin A. M., Sheahan B. J. 1995; Mechanisms of viral teratogenesis. Rev Med Virol 5:75–86 [View Article]
    [Google Scholar]
  11. Atkins G. J., Sheahan B. J., Liljeström P. 1999; The molecular pathogenesis of Semliki Forest virus: A model virus made useful?. J Gen Virol 80:2287–2297 [View Article][PubMed]
    [Google Scholar]
  12. Atkins G. J., Fleeton M. N., Sheahan B. J. 2008; Therapeutic and prophylactic applications of alphavirus vectors. Expert Rev Mol Med 10:e33 [View Article][PubMed]
    [Google Scholar]
  13. Balluz I. M., Glasgow G. M., Killen H. M., Mabruk M. J., Sheahan B. J., Atkins G. J. 1993; 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. Neuropathol Appl Neurobiol 19:233–239 [View Article][PubMed]
    [Google Scholar]
  14. Barrett P. N., Sheahan B. J., Atkins G. J. 1980; Isolation and preliminary characterization of Semliki Forest virus mutants with altered virulence. J Gen Virol 49:141–147 [View Article][PubMed]
    [Google Scholar]
  15. Barry G., Fragkoudis R., Ferguson M. C., Lulla A., Merits A., Kohl A., Fazakerley J. K. 2010; Semliki Forest virus-induced endoplasmic reticulum stress accelerates apoptotic death of mammalian cells. J Virol 84:7369–7377 [View Article][PubMed]
    [Google Scholar]
  16. Bernard K. A., Klimstra W. B., Johnston R. E. 2000; Mutations in the E2 glycoprotein of Venezuelan equine encephalitis virus confer heparan sulfate interaction, low morbidity, and rapid clearance from blood of mice. Virology 276:93–103 [View Article]
    [Google Scholar]
  17. Bianchi T. I., Aviles G., Monath T. P., Sabattini M. S. 1993; Western equine encephalomyelitis: Virulence markers and their epidemiologic significance. Am J Trop Med Hyg 49:322–328
    [Google Scholar]
  18. Bradish C. J., Allner K., Maber H. B. 1971; The virulence of original and derived strains of Semliki Forest virus for mice, guinea-pigs and rabbits. J Gen Virol 12:141–160 [View Article][PubMed]
    [Google Scholar]
  19. Britton P. N., Khandaker G., Booy R., Jones C. A. 2014; The causes and consequences of childhood encephalitis in Asia. Infect Disord Drug Targets 14: [View Article][PubMed]
    [Google Scholar]
  20. Burdeinick-Kerr R., Griffin D. E. 2005; Gamma interferon-dependent, noncytolytic clearance of Sindbis virus infection from neurons in vitro. J Virol 79:5374–5385 [View Article][PubMed]
    [Google Scholar]
  21. Burdeinick-Kerr R., Govindarajan D., Griffin D. E. 2009; Noncytolytic clearance of Sindbis virus infection from neurons by gamma interferon is dependent on Jak/Stat signaling. J Virol 83:3429–3435 [View Article][PubMed]
    [Google Scholar]
  22. Castorena K. M., Peltier D. C., Peng W., Miller D. J. 2008; Maturation-dependent responses of human neuronal cells to western equine encephalitis virus infection and type I interferons. Virology 372:208–220 [View Article]
    [Google Scholar]
  23. Charles P. C., Walters E., Margolis F., Johnston R. E. 1995; Mechanism of neuroinvasion of Venezuelan equine encephalitis virus in the mouse. Virology 208:662–671 [View Article]
    [Google Scholar]
  24. Das T., Jaffar-Bandjee M. C., Hoarau J. J., Krejbich Trotot P., Denizot M., Lee-Pat-Yuen G., Sahoo R., Guiraud P., Ramful D., other authors. 2010; Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus. Prog Neurobiol 91:121–129 [View Article][PubMed]
    [Google Scholar]
  25. Das T., Hoarau J. J., Jaffar Bandjee M. C., Maquart M., Gasque P. 2015; Multifaceted innate immune responses engaged by astrocytes, microglia and resident dendritic cells against chikungunya neuroinfection. J Gen Virol 96:294–310 [View Article][PubMed]
    [Google Scholar]
  26. Davis N. L., Willis L. V., Smith J. F., Johnston R. E. 1989; In vitro synthesis of infectious Venezuelan equine encephalitis virus RNA from a cDNA clone: Analysis of a viable deletion mutant. Virology 171:189–204 [View Article]
    [Google Scholar]
  27. Davis N. L., Powell N., Greenwald G. F., Willis L. V., Johnson B. J., Smith J. F., Johnston R. E. 1991; 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 183:20–31 [View Article]
    [Google Scholar]
  28. Davis N. L., Grieder F. B., Smith J. F., Greenwald G. F., Valenski M. L., Sellon D. C., Charles P. C., Johnston R. E. 1994; A molecular genetic approach to the study of Venezuelan equine encephalitis virus pathogenesis. Arch Virol 9:99–109 [View Article]
    [Google Scholar]
  29. Del Piero F., Wilkins P. A., Dubovi E. J., Biolatti B., Cantile C. 2001; Clinical, pathologic, immunohistochemical, and virologic findings of Eastern equine encephalomyelitis in two horses. Vet Pathol 38:451–456 [View Article][PubMed]
    [Google Scholar]
  30. Derlet R. W. 2014; Venezuelan equine encephalitis. http://emedicine.medscape.com/article/233913
  31. Deuber S. A., Pavlovic J. 2007; Virulence of a mouse-adapted Semliki Forest virus strain is associated with reduced susceptibility to interferon. J Gen Virol 88:1952–1959 [View Article][PubMed]
    [Google Scholar]
  32. Dropulic L. K., Hardwick J. M., Griffin D. E. 1997; A single amino acid change in the E2 glycoprotein of Sindbis virus confers neurovirulence by altering an early step of virus replication. J Virol 71:6100–6105[PubMed]
    [Google Scholar]
  33. Dubuisson J., Lustig S., Ruggli N., Akov Y., Rice C. M. 1997; Genetic determinants of Sindbis virus neuroinvasiveness. J Virol 71:2636–2646[PubMed]
    [Google Scholar]
  34. Fazakerley J. K., Webb H. E. 1987; Semliki Forest virus-induced, immune-mediated demyelination: Adoptive transfer studies and viral persistence in nude mice. J Gen Virol 68:377–385 [View Article][PubMed]
    [Google Scholar]
  35. Fazakerley J. K., Pathak S., Scallan M., Amor S., Dyson H. 1993; Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons. Virology 195:627–637 [View Article]
    [Google Scholar]
  36. Fazakerley J. K. 2002; Pathogenesis of Semliki Forest virus encephalitis. J Neurovirol 8:66–74 [View Article]
    [Google Scholar]
  37. Fazakerley J. K., Boyd A., Mikkola M. L., Kääriäinen L. 2002; A single amino acid change in the nuclear localization sequence of the nsP2 protein affects the neurovirulence of Semliki Forest virus. J Virol 76:392–396[PubMed]
    [Google Scholar]
  38. Fazakerley J. K. 2004; Semliki Forest virus infection of laboratory mice: A model to study the pathogenesis of viral encephalitis. Arch Virol Suppl 18:179–190[PubMed]
    [Google Scholar]
  39. Fazakerley J. K., Cotterill C. L., Lee G., Graham A. 2006; Virus tropism, distribution, persistence and pathology in the corpus callosum of the Semliki Forest virus-infected mouse brain: A novel system to study virus-oligodendrocyte interactions. Neuropathol Appl Neurobiol 32:397–409 [View Article][PubMed]
    [Google Scholar]
  40. Ferguson M. C., Saul S., Fragkoudis R., Weisheit S., Cox J., Patabendige A., Sherwood K., Watson M., Merits A., Fazakerley J. K. 2015; Ability of the encephalitic arbovirus Semliki Forest virus to cross the blood-brain barrier is determined by the charge of the E2 glycoprotein. J Virol 89:7536–7549 [View Article][PubMed]
    [Google Scholar]
  41. Fragkoudis R., Breakwell L., McKimmie C., Boyd A., Barry G., Kohl A., Merits A., Fazakerley J. K. 2007; The type I interferon system protects mice from Semliki Forest virus by preventing widespread virus dissemination in extraneural tissues, but does not mediate the restricted replication of avirulent virus in central nervous system neurons. J Gen Virol 88:3373–3384 [View Article][PubMed]
    [Google Scholar]
  42. Fragkoudis R., Tamberg N., Siu R., Kiiver K., Kohl A., Merits A., Fazakerley J. K. 2009; Neurons and oligodendrocytes in the mouse brain differ in their ability to replicate Semliki Forest virus. J Neurovirol 15:57–70 [View Article][PubMed]
    [Google Scholar]
  43. Galbraith S. E., Sheahan B. J., Atkins G. J. 2006; Deletions in the hypervariable domain of the nsP3 gene attenuate Semliki Forest virus virulence. J Gen Virol 87:937–947 [View Article][PubMed]
    [Google Scholar]
  44. Gardner C. L., Yin J., Burke C. W., Klimstra W. B., Ryman K. D. 2009; Type I interferon induction is correlated with attenuation of a South American Eastern equine encephalitis virus strain in mice. Virology 390:338–347 [View Article]
    [Google Scholar]
  45. Gardner C. L., Ebel G. D., Ryman K. D., Klimstra W. B. 2011; Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence. Proc Natl Acad Sci U S A 108:16026–16031 [View Article][PubMed]
    [Google Scholar]
  46. Gardner C. L., Choi-Nurvitadhi J., Sun C., Bayer A., Hritz J., Ryman K. D., Klimstra W. B. 2013; Natural variation in the heparan sulfate binding domain of the eastern equine encephalitis virus E2 glycoprotein alters interactions with cell surfaces and virulence in mice. J Virol 87:8582–8590 [View Article][PubMed]
    [Google Scholar]
  47. Gates M. C., Sheahan B. J., Atkins G. J. 1984; The pathogenicity of the M9 mutant of Semliki Forest virus in immune-compromised mice. J Gen Virol 65:73–80
    [Google Scholar]
  48. Gates M. C., Sheahan B. J., O'Sullivan M. A., Atkins G. J. 1985; The pathogenicity of the A7, M9 and L10 strains of Semliki Forest virus for weanling mice and primary mouse brain cell cultures. J Gen Virol 66:2365–2373 [View Article][PubMed]
    [Google Scholar]
  49. Glasgow G. M., Sheahan B. J., Atkins G. J., Wahlberg J. M., Salminen A., Liljeström P. 1991; 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 185:741–748 [View Article]
    [Google Scholar]
  50. Glasgow G. M., Killen H. M., Liljeström P., Sheahan B. J., Atkins G. J. 1994; A single amino acid change in the E2 spike protein of a virulent strain of Semliki Forest virus attenuates pathogenicity. J Gen Virol 75:663–668 [View Article][PubMed]
    [Google Scholar]
  51. Glasgow G. M., McGee M. M., Sheahan B. J., Atkins G. J. 1997; Death mechanisms in cultured cells infected by Semliki Forest virus. J Gen Virol 78:1559–1563 [View Article][PubMed]
    [Google Scholar]
  52. Glasgow G. M., McGee M. M., Tarbatt C. J., Mooney D. A., Sheahan B. J., Atkins G. J. 1998; The Semliki Forest virus vector induces p53-independent apoptosis. J Gen Virol 79:2405–2410 [View Article][PubMed]
    [Google Scholar]
  53. Grandgirard D., Studer E., Monney L., Belser T., Fellay I., Borner C., Michel M. R. 1998; Alphaviruses induce apoptosis in Bcl-2-overexpressing cells: evidence for a caspase-mediated, proteolytic inactivation of Bcl-2. EMBO J 17:1268–1278 [View Article]
    [Google Scholar]
  54. Greene I. P., Paessler S., Austgen L., Anishchenko M., Brault A. C., Bowen R. A., Weaver S. C. 2005; Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic Venezuelan equine encephalitis virus. J Virol 79:9128–9133 [View Article]
    [Google Scholar]
  55. Grieder F. B., Davis N. L., Aronson J. F., Charles P. C., Sellon D. C., Suzuki K., Johnston R. E, Knott T., Brown K. 1995; Specific restrictions in the progression of Venezuelan equine encephalitis virus-induced disease resulting from single amino acid changes in the glycoproteins. Virology 206:994–1006 [View Article]
    [Google Scholar]
  56. Griffin D. E. 2001; Alphaviruses. In Fields Virology, 4th edn,. pp. 917–962 Edited by Knipe D. M, Howley P. M. Philadelphia, PA:: Lippincott, Williams & Wilkins;
    [Google Scholar]
  57. Hahn C. S., Lustig S., Strauss E. G., Strauss J. H. 1988; Western equine encephalitis virus is a recombinant virus. Proc Natl Acad Sci U S A 85:5997–6001 [View Article][PubMed]
    [Google Scholar]
  58. Heise M. T., Simpson D. A., Johnston R. E. 2000; A single amino acid change in nsP1 attenuates neurovirulence of the Sindbis-group alphavirus S.A.AR86. J Virol 74:4207–4213 [View Article][PubMed]
    [Google Scholar]
  59. Heise M. T., White L. J., Simpson D. A., Leonard C., Bernard K. A., Meeker R. B., Johnston R. E. 2003; An attenuating mutation in nsP1 of the Sindbis-group virus S.A.AR86 accelerates nonstructural protein processing and up-regulates viral 26S RNA synthesis. J Virol 77:1149–1156 [View Article][PubMed]
    [Google Scholar]
  60. Inglis F. M., Lee K. M., Chiu K. B., Purcell O. M., Didier P. J., Russell-Lodrigue K., Weaver S. C., Roy C. J., MacLean A. G. 2016; Neuropathogenesis of Chikungunya infection: Astrogliosis and innate immune activation. J Neurovirol 22: [View Article][PubMed]
    [Google Scholar]
  61. Jackson A. C., Rossiter J. P. 1997; Apoptotic cell death is an important cause of neuronal injury in experimental Venezuelan equine encephalitis virus infection of mice. Acta Neuropathol 93:349–353 [View Article][PubMed]
    [Google Scholar]
  62. Jan J. T., Griffin D. E. 1999; Induction of apoptosis by Sindbis virus occurs at cell entry and does not require virus replication. J Virol 73:10296–10302[PubMed]
    [Google Scholar]
  63. Johnson B. J., Kinney R. M., Kost C. L., Trent D. W. 1986; Molecular determinants of alphavirus neurovirulence: Nucleotide and deduced protein sequence changes during attenuation of Venezuelan equine encephalitis virus. J Gen Virol 67:1951–1960 [View Article][PubMed]
    [Google Scholar]
  64. Julander J. G., Siddharthan V., Blatt L. M., Schafer K., Sidwell R. W., Morrey J. D. 2007; Effect of exogenous interferon and an interferon inducer on Western equine encephalitis virus disease in a hamster model. Virology 360:454–460 [View Article]
    [Google Scholar]
  65. Kerr D. A., Larsen T., Cook S. H., Fannjiang Y. R., Choi E., Griffin D. E., Hardwick J. M., Irani D. N. 2002; BCL-2 and BAX protect adult mice from lethal Sindbis virus infection but do not protect spinal cord motor neurons or prevent paralysis. J Virol 76:10393–10400 [View Article][PubMed]
    [Google Scholar]
  66. Kulcsar K. A., Baxter V. K., Abraham R., Nelson A., Griffin D. E. 2015; Distinct immune responses in resistant and susceptible strains of mice during neurovirulent alphavirus encephalomyelitis. J Virol 89:8280–8291 [View Article][PubMed]
    [Google Scholar]
  67. Kümmerer B. M., Grywna K., Gläsker S., Wieseler J., Drosten C. 2012; Construction of an infectious Chikungunya virus cDNA clone and stable insertion of mCherry reporter genes at two different sites. J Gen Virol 93:1991–1005 [View Article][PubMed]
    [Google Scholar]
  68. Lee P., Knight R., Smit J. M., Wilschut J., Griffin D. E. 2002; A single mutation in the E2 glycoprotein important for neurovirulence influences binding of Sindbis virus to neuroblastoma cells. J Virol 76:6302–6310 [View Article][PubMed]
    [Google Scholar]
  69. Levine B., Hardwick, Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. 1991; Antibody-mediated clearance of alphavirus infection from neurons. Science 254:856–860 [View Article]
    [Google Scholar]
  70. Levine B., Huang Q., Isaacs J. T., Reed J. C., Griffin D. E., Hardwick J. M. 1993; Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature 361:739–742 [View Article]
    [Google Scholar]
  71. Lewis J., Wesselingh S. L., Griffin D. E., Hardwick J. M. 1996; Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence. J Virol 70:1828–1835[PubMed]
    [Google Scholar]
  72. Lewis J., Oyler G. A., Ueno K., Fannjiang Y. R., Chau B. N., Vornov J., Korsmeyer S. J., Zou S., Hardwick J. M., Yomov J. 1999; Inhibition of virus-induced neuronal apoptosis by Bax. Nat Med 5:832–835 [View Article][PubMed]
    [Google Scholar]
  73. Li L., Jose J., Xiang Y., Kuhn R. J., Rossmann M. G. 2010; Structural changes of envelope proteins during alphavirus fusion. Nature 468:705–708 [View Article]
    [Google Scholar]
  74. Liljeström P., Lusa S., Huylebroeck D., Garoff H. 1991; In vitro mutagenesis of a full-length cDNA clone of Semliki Forest virus: The small 6,000-molecular-weight membrane protein modulates virus release. J Virol 65:4107–4113[PubMed]
    [Google Scholar]
  75. Logue C. H., Powers A. M. 2007; Changing patterns of Chikungunya virus: Re emergence of a zoonotic arbovirus. J Gen Virol 88:2363–2377 [View Article][PubMed]
    [Google Scholar]
  76. Logue C. H., Sheahan B. J., Atkins G. J. 2008; The 5′ untranslated region as a pathogenicity determinant of Semliki Forest virus in mice. Virus Genes 36:313–321 [View Article][PubMed]
    [Google Scholar]
  77. Logue C. H., Bosio C. F., Welte T., Keene K. M., Ledermann J. P., Phillips A., Sheahan B. J., Pierro D. J., Marlenee N., Brault A. C., other authors. 2009; Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model. J Gen Virol 90:1848–1858 [View Article][PubMed]
    [Google Scholar]
  78. Lundstrom K., Pralong W., Martinou J. C. 1997; Anti-apoptotic effect of Bcl-2 overexpression in RIN cells infected with Semliki Forest virus. Apoptosis 2:189–191 [View Article][PubMed]
    [Google Scholar]
  79. Lustig S., Jackson A. C., Hahn C. S., Griffin D. E., Strauss E. G., Strauss J. H. 1988; Molecular basis of Sindbis virus neurovirulence in mice. J Virol 62:2329–2336[PubMed]
    [Google Scholar]
  80. MacDonald G. H., Johnston R. E. 2000; Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis. J Virol 74:914–922 [View Article][PubMed]
    [Google Scholar]
  81. Martikainen M., Niittykoski M., von und zu Fraunberg M., Immonen A., Koponen S., van Geenen M., Vähä-Koskela M., Ylösmäki E., Jääskeläinen J. E., Saksela K., other authors. 2015; MicroRNA-attenuated clone of virulent Semliki Forest virus overcomes antiviral type I interferon in resistant mouse CT-2A glioma. J Virol 89:10637–10647 [View Article][PubMed]
    [Google Scholar]
  82. Mathiot C. C., Bouquety J. C., Daquisy A. M., Bouquety J. C., Mada A., Daquisy A. M., Georges A. 1990; An outbreak of human Semliki Forest virus infections in Central African Republic. Am J Trop Med Hyg 42:386–393
    [Google Scholar]
  83. McIntosh B. M., Brooke Worth C., Kokernot R. H. 1961; Isolation of Semliki Forest virus from Aedes (Aedimorphus) argenteopunctatus (theobald) collected in Portuguese East Africa. Trans R Soc Trop Med Hyg 55:192–198[PubMed]
    [Google Scholar]
  84. Mossel E. C., Ledermann J. P., Phillips A. T., Borland E. M., Powers A. M., Olson K. E. 2013; Molecular determinants of mouse neurovirulence and mosquito infection for Western equine encephalitis virus. PLoS One 8:e60427 [View Article][PubMed]
    [Google Scholar]
  85. Murphy A. M., Sheahan B. J., Atkins G. J. 2001; Induction of apoptosis in Bcl-2-expressing rat prostate cancer cells using the Semliki Forest virus vector. Int J Cancer 94:572–578 [View Article][PubMed]
    [Google Scholar]
  86. Nagata L. P., Hu W. G., Parker M., Chau D., Rayner G. A., Schmaltz F. L., Wong J. P. 2006; Infectivity variation and genetic diversity among strains of Western equine encephalitis virus. J Gen Virol 87:2353–2361 [View Article][PubMed]
    [Google Scholar]
  87. Nava V. E., Rosen A., Veliuona M. A., Clem R. J., Levine B., Hardwick J. M. 1998; Sindbis virus induces apoptosis through a caspase-dependent, CrmA-sensitive pathway. J Virol 72:452–459[PubMed]
    [Google Scholar]
  88. Netolitzky D. J., Schmaltz F. L., Parker M. D., Rayner G. A., Fisher G. R., Trent D. W., Bader D. E., Nagata L. P. 2000; Complete genomic RNA sequence of western equine encephalitis virus and expression of the structural genes. J Gen Virol 81:151–159 [View Article][PubMed]
    [Google Scholar]
  89. Oliver K. R., Scallan M. F., Dyson H., Fazakerley J. K. 1997; Susceptibility to a neurotropic virus and its changing distribution in the developing brain is a function of CNS maturity. J Neurovirol 3:38–48 [View Article][PubMed]
    [Google Scholar]
  90. Peltier D. C., Lazear H. M., Farmer J. R., Diamond M. S., Miller D. J. 2013; Neurotropic arboviruses induce interferon regulatory factor 3-mediated neuronal responses that are cytoprotective, interferon independent, and inhibited by Western equine encephalitis virus capsid. J Virol 87:1821–1833 [View Article][PubMed]
    [Google Scholar]
  91. Polo J. M., Davis N. L., Rice C. M., Huang H. V., Johnston R. E. 1988; Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro. J Virol 62:2124–2133[PubMed]
    [Google Scholar]
  92. Powers A. M., Logue C. H. 2007; Changing patterns of Chikungunya virus: Re-emergence of a zoonotic arbovirus. J Gen Virol 88:2363–2377 [View Article][PubMed]
    [Google Scholar]
  93. Rupp J. C., Sokoloski K. J., Gebhart N. N., Hardy R. W. 2015; Alphavirus RNA synthesis and non-structural protein functions. J Gen Virol 96:2483–2500 [View Article][PubMed]
    [Google Scholar]
  94. Ryman K. D., Gardner C. L., Burke C. W., Meier K. C., Thompson J. M., Klimstra W. B. 2007; Heparan sulfate binding can contribute to the neurovirulence of neuroadapted and nonneuroadapted Sindbis viruses. J Virol 81:3563–3573 [View Article][PubMed]
    [Google Scholar]
  95. Sammin D. J., Butler D., Atkins G. J., Sheahan B. J. 1999; Cell death mechanisms in the olfactory bulb of rats infected intranasally with Semliki Forest virus. Neuropathol Appl Neurobiol 25:236–243 [View Article][PubMed]
    [Google Scholar]
  96. Santagati M. G., Määttä J. A., Itäranta P. V., Salmi A. A., Hinkkanen A. E. 1995; The Semliki Forest virus E2 gene as a virulence determinant. J Gen Virol 76:47–52 [View Article][PubMed]
    [Google Scholar]
  97. Santagati M. G., Määttä J. A., Röyttä M., Salmi A. A., Hinkkanen A. E. 1998; The significance of the 3′-nontranslated region and E2 amino acid mutations in the virulence of Semliki Forest virus in mice. Virology 243:66–77 [View Article]
    [Google Scholar]
  98. Saul S., Ferguson M., Cordonin C., Fragkoudis R., Ool M., Tamberg N., Sherwood K., Fazakerley J. K., Merits A. 2015; Differences in processing determinants of nonstructural polyprotein and in the sequence of nonstructural protein 3 affect neurovirulence of Semliki Forest virus. J Virol 89:11030–11045 [View Article][PubMed]
    [Google Scholar]
  99. Scallan M. F., Allsopp T. E., Fazakerley J. K. 1997; Bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death. J Virol 71:1583–1590[PubMed]
    [Google Scholar]
  100. Schultz K. L. W., Vernon P. S., Griffin D. E. 2015; Differentiation of neurons restricts arbovirus replication and increases expression of the alpha isoform of IRF-7. J Virol 89:48–60 [View Article]
    [Google Scholar]
  101. Schäfer A., Brooke C. B., Whitmore A. C., Johnston R. E. 2011; The role of the blood-brain barrier during Venezuelan equine encephalitis virus infection. J Virol 85:10682–10690 [View Article][PubMed]
    [Google Scholar]
  102. Shaikh N. J., Raut C. G., Siinha D. P., Manjunath M. J. 2015; Detection of Chikungunya virus from a case of encephalitis, Bangalore, Karnataka State. Ind J Med Microbiol 33:454–455
    [Google Scholar]
  103. Sheahan B. J., Gates M. C., Caffrey J. F., Atkins G. J. 1983; Oligodendrocyte infection and demyelination produced in mice by the M9 mutant of Semliki Forest virus. Acta Neuropathol 60:257–265 [View Article][PubMed]
    [Google Scholar]
  104. Sheahan B. J., Ibrahim M. A., Atkins G. J. 1996; Demyelination of olfactory pathways in mice following intranasal infection with the avirulent A7 strain of Semliki Forest virus. Eur J Vet Pathol 2:117–125
    [Google Scholar]
  105. Simmons J. D., Wollish A. C., Heise M. T. 2010; A determinant of sindbis virus neurovirulence enables efficient disruption of Jak/Stat signaling. J Virol 84:11429–11439 [View Article][PubMed]
    [Google Scholar]
  106. Smithburn K. C., Haddow W. J. 1944; Semliki Forest virus - I - isolation and pathogenic properties. J Immunol 49:141–145
    [Google Scholar]
  107. Smithburn K. C., Haddow W. J., Mahaffy A. F. 1946; A neurotropic virus isolated from Aedes mosquitoes caught in the Semliki Forest. Am J Trop Med Hyg 26:189–208
    [Google Scholar]
  108. Subak-Sharpe I., Dyson H., Fazakerley J. 1993; In vivo depletion of CD8+ T cells prevents lesions of demyelination in Semliki Forest virus infection. J Virol 67:7629–7633[PubMed]
    [Google Scholar]
  109. Suthar M. S., Shabman R., Madric K., Lambeth C., Heise M. T. 2005; Identification of adult mouse neurovirulence determinants of the Sindbis virus strain AR86. J Virol 79:4219–4228 [View Article][PubMed]
    [Google Scholar]
  110. Taraphdar D., Roy B. K., Chatterjee S. 2015; Chikungunya virus infection amongst the acute encephalitis cases in West Bengal, India. Ind J Med Microbiol Suppl 33:153–156
    [Google Scholar]
  111. Tarbatt C. J., Glasgow G. M., Mooney D. A., Sheahan B. J., Atkins G. J. 1997; Sequence analysis of the avirulent, demyelinating A7 strain of Semliki Forest virus. J Gen Virol 78:1551–1557 [View Article][PubMed]
    [Google Scholar]
  112. Taylor A., Herrero L. J., Rudd P. A., Mahalingam S. 2015; Mouse models of alphavirus-induced inflammatory disease. J Gen Virol 96:221–238 [View Article][PubMed]
    [Google Scholar]
  113. Tucker P. C., Strauss E. G., Kuhn R. J., Strauss J. H., Griffin D. E. 1993; Viral determinants of age-dependent virulence of Sindbis virus for mice. J Virol 67:4605–4610[PubMed]
    [Google Scholar]
  114. Tucker P. C., Lee S. H., Bui N., Martinie D., Griffin D. E. 1997; Amino acid changes in the Sindbis virus E2 glycoprotein that increase neurovirulence improve entry into neuroblastoma cells. J Virol 71:6106–6112[PubMed]
    [Google Scholar]
  115. Tuittila M. T., Santagati M. G., Röyttä M., Määttä J. A., Hinkkanen A. E. 2000; Replicase complex genes of Semliki Forest virus confer lethal neurovirulence. J Virol 74:4579–4589[PubMed]
    [Google Scholar]
  116. Tuittila M., Hinkkanen A. E. 2003; Amino acid mutations in the replicase protein nsP3 of Semliki Forest virus cumulatively affect neurovirulence. J Gen Virol 84:1525–1533 [View Article][PubMed]
    [Google Scholar]
  117. Ubol S., Tucker P. C., Griffin D. E., Hardwick J. M. 1994; Neurovirulent strains of alphavirus induce apoptosis in bcl-2-expressing cells: Role of a single amino acid change in the E2 glycoprotein. Proc Natl Acad Sci U S A 91:5202–5206 [View Article][PubMed]
    [Google Scholar]
  118. Vernon P. S., Griffin D. E. 2005; Characterization of an in vitro model of alphavirus infection of immature and mature neurons. J Virol 79:3438–3447 [View Article][PubMed]
    [Google Scholar]
  119. Voss J. E., Vaney M.-C., Duquerroy S., Vonrhein C., Girard-Blanc C., Crublet E., Thompson A., Bricogne G., Rey F. A. 2010; Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature 468:709–712 [View Article]
    [Google Scholar]
  120. Wang E., Volkova E., Adams A. P., Forrester N., Xiao S. Y., Frolov I., Weaver S. C. 2008; Chimeric alphavirus vaccine candidates for Chikungunya. Vaccine 26:5030–5039 [View Article][PubMed]
    [Google Scholar]
  121. Weaver S. C., Hagenbaugh A., Bellew L. A., Netesov S. V., Volchkov V. E., Chang G.-J. J., Clarke D. K., Gousset L., Scott T. W., Trent D. W. 1993; A comparison of the nucleotide sequences of Eastern and Western equine encephalomyelitis viruses with those of other alphaviruses and related RNA viruses. Virology 197:375–390 [View Article]
    [Google Scholar]
  122. Weaver S. C., Kang W., Shirako Y., Rumenapf T., Strauss E. G., Strauss J. H. 1997; Recombinational history and molecular evolution of western equine encephalomyelitis complex alphaviruses. J Virol 71:613–623[PubMed]
    [Google Scholar]
  123. Weaver S. C., Ferro C., Barrera R., Boshell J., Navarro J. C. 2004; Venezuelan Equine Encephalitis. Annu Rev Entomol 49:141–174
    [Google Scholar]
  124. Weaver S. C., Reisen W. K. 2010; Present and future arboviral threats. Antiviral Res 85:328–345 [View Article][PubMed]
    [Google Scholar]
  125. Weger-Lucarelli J., Aliota M. T., Wlodarchak N., Kamlangdee A., Swanson R., Osorio J. E. 2016; Dissecting the role of E2 protein domains in alphavirus pathogenicity. J Virol 90:2418–2433 [View Article]
    [Google Scholar]
  126. White L. J., Wang J. G., Davis N. L., Johnston R. E. 2001; Role of alpha/beta interferon in Venezuelan equine encephalitis virus pathogenesis: Effect of an attenuating mutation in the 5′ untranslated region. J Virol 75:3706–3718 [View Article][PubMed]
    [Google Scholar]
  127. Willems W. R., Kaluza G., Boschek C. B., Bauer H., Hager H., Schutz H., Feistner H. 1979; Semliki Forest virus: Cause of a fatal case of human encephalitis. Science 203:1127–1129 [View Article]
    [Google Scholar]
  128. Williams S. M., Fulton R. M., Patterson J. S., Reed W. M. 2000; Diagnosis of Eastern equine encephalitis by immunohistochemistry in two flocks of Michigan ring-neck pheasants. Avian Dis 44:1012–1016 [View Article][PubMed]
    [Google Scholar]
  129. Wollish A. C., Ferris M. T., Blevins L. K., Loo Y. -M., Gale M., Heise M. T. 2013; An attenuating mutation in a neurovirulent Sindbis virus strain interacts with the ISP-1 signaling pathway in vivo. Virology 435:269–280 [View Article]
    [Google Scholar]
  130. Ylösmäki E., Martikainen M., Hinkkanen A., Saksela K. 2013; Attenuation of Semliki Forest virus neurovirulence by MicroRNA-mediated detargeting. J Virol 87:335–344 [View Article][PubMed]
    [Google Scholar]
  131. Zacks M. A., Paessler S. 2010; Encephalitic alphaviruses. Vet Microbiol 140:281–286 [View Article][PubMed]
    [Google Scholar]
  132. Zhu W., Deng L., Wei Y., Wang H., Wang J., Liang G. 2015; A substitution in nsP1 combined with a double substitution in E2 glycoprotein renders Sindbis-like virus XJ-160 fully neurovirulent for adult mice. Virus Res 196:1–4 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000467
Loading
/content/journal/jgv/10.1099/jgv.0.000467
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error