1887

Abstract

Two New York (NY) strains of the West Nile (WN) virus were plaque-purified and four variants that had different amino acid sequences at the -linked glycosylation site in the envelope (E) protein sequence were isolated. The E protein was glycosylated in only two of these strain variants. To determine the relationship between E protein glycosylation and pathogenicity of the WN virus, 6-week-old mice were infected subcutaneously with these variants. Mice infected with viruses that carried the glycosylated E protein developed lethal infection, whereas mice infected with viruses that carried the non-glycosylated E protein showed low mortality. In contrast, intracerebral infection of mice with viruses carrying either the glycosylated or non-glycosylated forms of the E protein resulted in lethal infection. These results suggested that E protein glycosylation is a molecular determinant of neuroinvasiveness in the NY strains of WN virus.

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2004-12-01
2024-12-07
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References

  1. Anderson J. F., Vossbrinck C. R., Andreadis T. G., Iton A., Beckwith W. H. III, Mayo D. R. 2001; A phylogenetic approach to following West Nile virus in Connecticut. Proc Natl Acad Sci U S A 98:12885–12889 [CrossRef]
    [Google Scholar]
  2. Beasley D. W. C., Li L., Suderman M. T., Barrett A. D. T. 2002; Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype. Virology 296:17–23 [CrossRef]
    [Google Scholar]
  3. Chambers T. J., Hahn C. S., Galler R., Rice C. M. 1990; Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44:649–688 [CrossRef]
    [Google Scholar]
  4. Chambers T. J., Halevy M., Nestorowicz A., Rice C. M., Lustig S. 1998; West Nile virus envelope proteins: nucleotide sequence analysis of strains differing in mouse neuroinvasiveness. J Gen Virol 79:2375–2380
    [Google Scholar]
  5. Diamond M. S., Shrestha B., Marri A., Mahan D., Engle M. 2003; B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus. J Virol 77:2578–2586 [CrossRef]
    [Google Scholar]
  6. Falgout B., Pethel M., Zhang Y.-M., Lai C.-J. 1991; Both nonstructural proteins NS2B and NS3 are required for the proteolytic processing of dengue virus nonstructural proteins. J Virol 65:2467–2475
    [Google Scholar]
  7. Garmendia A. E., Van Kruiningen H. J., French R. A. 2001; The West Nile virus: its recent emergence in North America. Microbes Infect 3:223–229 [CrossRef]
    [Google Scholar]
  8. Halevy M., Akov Y., Ben-Nathan D., Kobiler D., Lachmi B., Lustig S. 1994; Loss of active neuroinvasiveness in attenuated strains of West Nile virus: pathogenicity in immunocompetent and SCID mice. Arch Virol 137:355–370 [CrossRef]
    [Google Scholar]
  9. Hamman M. H., Delphine H. C., Winston H. P. 1965; Antigenic variation of West Nile virus in relation to geography. Am J Epidemiol 82:40–55
    [Google Scholar]
  10. Hubálek Z., Halouzka J. 1999; West Nile fever – a reemerging mosquito-borne viral disease in Europe. Emerg Infect Dis 5:643–650 [CrossRef]
    [Google Scholar]
  11. Johnston L. J., Halliday G. M., King N. J. C. 2000; Langerhans cells migrate to local lymph nodes following cutaneous infection with an arbovirus. J Invest Dermatol 114:560–568 [CrossRef]
    [Google Scholar]
  12. Kolykhalov A. A., Feinstone S. M., Rice C. M. 1996; Identification of a highly conserved sequence element at the 3′ terminus of hepatitis C virus genome RNA. J Virol 70:3363–3371
    [Google Scholar]
  13. Lad V. J., Shende V. R., Gupta A. K., Koshy A. A., Roy A. 2000; Effect of tunicamycin on expression of epitopes on Japanese encephalitis virus glycoprotein E in porcine kidney cells. Acta Virol 44:359–364
    [Google Scholar]
  14. Li H., Clum S., You S., Ebner K. E., Padmanabhan R. 1999; The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids. J Virol 73:3108–3116
    [Google Scholar]
  15. Licon Luna R. M., Lee E., Müllbacher A., Blanden R. V., Langman R., Lobigs M. 2002; Lack of both Fas ligand and perforin protects from flavivirus-mediated encephalitis in mice. J Virol 76:3202–3211 [CrossRef]
    [Google Scholar]
  16. Lo M. K., Tilgner M., Bernard K. A., Shi P.-Y. 2003; Functional analysis of mosquito-borne flavivirus conserved sequence elements within 3′ untranslated region of West Nile virus by use of a reporting replicon that differentiates between viral translation and RNA replication. J Virol 77:10004–10014 [CrossRef]
    [Google Scholar]
  17. Matusan A. E., Pryor M. J., Davidson A. D., Wright P. J. 2001; Mutagenesis of the Dengue virus type 2 NS3 protein within and outside helicase motifs: effects on enzyme activity and virus replication. J Virol 75:9633–9643 [CrossRef]
    [Google Scholar]
  18. Scherret J. H., Mackenzie J. S., Khromykh A. A., Hall R. A. 2001; Biological significance of glycosylation of the envelope protein of Kunjin virus. Ann N Y Acad Sci 951:361–363
    [Google Scholar]
  19. Seligman S. J., Bucher D. J. 2003; The importance of being outer: consequences of the distinction between the outer and inner surfaces of flavivirus glycoprotein E. Trends Microbiol 11:108–110 [CrossRef]
    [Google Scholar]
  20. Shi P.-Y., Brinton M. A., Veal J. M., Zhong Y. Y., Wilson W. D. 1996; Evidence for the existence of a pseudoknot structure at the 3′ terminus of the flavivirus genomic RNA. Biochemistry 35:4222–4230 [CrossRef]
    [Google Scholar]
  21. Shirato K., Mizutani T., Kariwa H., Takashima I. 2003; Discrimination of West Nile virus and Japanese encephalitis virus strains using RT-PCR RFLP analysis. Microbiol Immunol 47:439–445 [CrossRef]
    [Google Scholar]
  22. Tilgner M., Shi P.-Y. 2004; Structure and function of the 3′ terminal six nucleotides of the West Nile virus genome in viral replication. J Virol 78:8159–8171 [CrossRef]
    [Google Scholar]
  23. Timofeev A. V., Butenko V. M., Stephenson J. R. 2004; Genetic vaccination of mice with plasmids encoding the NS1 non-structural protein from tick-borne encephalitis virus and dengue 2 virus. Virus Genes 28:85–97 [CrossRef]
    [Google Scholar]
  24. Wang T., Anderson J. F., Magnarelli L. A., Bushmich S., Wong S., Koski R. A., Fikrig E. 2001a; West Nile virus envelope protein: role in diagnosis and immunity. Ann N Y Acad Sci 951:325–327
    [Google Scholar]
  25. Wang T., Anderson J. F., Magnarelli L. A., Wong S. J., Koski R. A., Fikrig E. 2001b; Immunization of mice against West Nile virus with recombinant envelope protein. J Immunol 167:5273–5277 [CrossRef]
    [Google Scholar]
  26. Wang T., Scully E., Yin Z. 7 other authors 2003a; IFN- γ -producing γδ T cells help control murine West Nile virus infection. J Immunol 171:2524–2531 [CrossRef]
    [Google Scholar]
  27. Wang Y., Lobigs M., Lee E., Müllbacher A. 2003b; CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis. J Virol 77:13323–13334 [CrossRef]
    [Google Scholar]
  28. Wu S.-J. L., Grouard-Vogel G., Sun W. 14 other authors 2000; Human skin Langerhans cells are targets of dengue virus infection. Nat Med 6:816–820 [CrossRef]
    [Google Scholar]
  29. Xu G., Xu X., Li Z., He Q., Wu B., Sun S., Chen H. 2004; Construction of recombinant pseudorabies virus expressing NS1 protein of Japanese encephalitis (SA14-14-2) virus and its safety and immunogenicity. Vaccine 22:1846–1853 [CrossRef]
    [Google Scholar]
  30. Yun S.-I., Kim S.-Y., Rice C. M., Lee Y.-M. 2003; Development and application of a reverse genetics system for Japanese encephalitis virus. J Virol 77:6450–6465 [CrossRef]
    [Google Scholar]
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