1887

Abstract

Japanese encephalitis virus (JEV), which belongs to the genus of the family , is a leading cause of meningo-encephalitis in Asian countries. The flavivirus non-structural protein 1 (NS1) plays a role in virus replication and in the elicitation of an immune response. The NS1′ protein found among the members of the JEV subgroup is an extended form of NS1 and is generated by a −1 ribosomal frameshift. This protein is known to be involved in viral pathogenicity; however, its specific function is still unknown. Here, we describe an investigation of the molecular function of NS1′ protein through the production of JEV NS1′-expressing and -non-expressing clones and their infection of avian and mammalian cells. Efficient NS1′ protein expression was observed in avian cells and was found to facilitate JEV production in both avian cultured cells and embryonated chicken eggs. NS1′ protein was observed to co-localize with NS5 protein and resulted in increased viral RNA levels in avian cells. These findings clearly indicate that NS1′ enhances the production of JEV in avian cells and may facilitate the amplification/maintenance role of birds in the virus transmission cycle in nature.

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2014-02-01
2024-12-05
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References

  1. Avirutnan P., Fuchs A., Hauhart R. E., Somnuke P., Youn S., Diamond M. S., Atkinson J. P. 2010; Antagonism of the complement component C4 by flavivirus nonstructural protein NS1. J Exp Med 207:793–806 [View Article][PubMed]
    [Google Scholar]
  2. Blitvich B. J., MacKenzie J. S., Coelen R. J., Howard M. J., Hall R. A. 1995; A novel complex formed between the flavivirus E and NS1 proteins: analysis of its structure and function. Arch Virol 140:145–156 [View Article][PubMed]
    [Google Scholar]
  3. Brierley I., Pennell S., Gilbert R. J. 2007; Viral RNA pseudoknots: versatile motifs in gene expression and replication. Nat Rev Microbiol 5:598–610 [View Article][PubMed]
    [Google Scholar]
  4. Chen L. K., Liao C. L., Lin C. G., Lai S. C., Liu C. I., Ma S. H., Huang Y. Y., Lin Y. L. 1996; Persistence of Japanese encephalitis virus is associated with abnormal expression of the nonstructural protein NS1 in host cells. Virology 217:220–229 [View Article][PubMed]
    [Google Scholar]
  5. Chung K. M., Liszewski M. K., Nybakken G., Davis A. E., Townsend R. R., Fremont D. H., Atkinson J. P., Diamond M. S. 2006a; West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H. Proc Natl Acad Sci U S A 103:19111–19116 [View Article][PubMed]
    [Google Scholar]
  6. Chung K. M., Nybakken G. E., Thompson B. S., Engle M. J., Marri A., Fremont D. H., Diamond M. S. 2006b; Antibodies against West Nile virus nonstructural protein NS1 prevent lethal infection through Fc γ receptor-dependent and -independent mechanisms. J Virol 80:1340–1351 [View Article][PubMed]
    [Google Scholar]
  7. Chung K. M., Thompson B. S., Fremont D. H., Diamond M. S. 2007; Antibody recognition of cell surface-associated NS1 triggers Fc-γ receptor-mediated phagocytosis and clearance of West Nile virus-infected cells. J Virol 81:9551–9555 [View Article][PubMed]
    [Google Scholar]
  8. Clavijo A., Heckert R. A., Dulac G. C., Afshar A. 2000; Isolation and identification of bluetongue virus. J Virol Methods 87:13–23 [View Article][PubMed]
    [Google Scholar]
  9. Crespo R., Shivaprasad H. L., França M., Woolcock P. R. 2009; Isolation and distribution of West Nile virus in embryonated chicken eggs. Avian Dis 53:608–612 [View Article][PubMed]
    [Google Scholar]
  10. Espada-Murao L. A., Morita K. 2011; Delayed cytosolic exposure of Japanese encephalitis virus double-stranded RNA impedes interferon activation and enhances viral dissemination in porcine cells. J Virol 85:6736–6749 [View Article][PubMed]
    [Google Scholar]
  11. Ferreira V. P., Pangburn M. K., Cortés C. 2010; Complement control protein factor H: the good, the bad, and the inadequate. Mol Immunol 47:2187–2197 [View Article][PubMed]
    [Google Scholar]
  12. Firth A. E., Atkins J. F. 2009; A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1′ may derive from ribosomal frameshifting. Virol J 6:14 [View Article][PubMed]
    [Google Scholar]
  13. Fujii Y., Kitaura K., Nakamichi K., Takasaki T., Suzuki R., Kurane I. 2008; Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice. Jpn J Infect Dis 61:40–48[PubMed]
    [Google Scholar]
  14. Ghosh D., Basu A. 2009; Japanese encephalitis – a pathological and clinical perspective. PLoS Negl Trop Dis 3:e437 [View Article][PubMed]
    [Google Scholar]
  15. Hayasaka D., Gritsun T. S., Yoshii K., Ueki T., Goto A., Mizutani T., Kariwa H., Iwasaki T., Gould E. A., Takashima I. 2004; Amino acid changes responsible for attenuation of virus neurovirulence in an infectious cDNA clone of the Oshima strain of tick-borne encephalitis virus. J Gen Virol 85:1007–1018 [View Article][PubMed]
    [Google Scholar]
  16. Hayasaka D., Nagata N., Fujii Y., Hasegawa H., Sata T., Suzuki R., Gould E. A., Takashima I., Koike S. 2009; Mortality following peripheral infection with tick-borne encephalitis virus results from a combination of central nervous system pathology, systemic inflammatory and stress responses. Virology 390:139–150 [View Article][PubMed]
    [Google Scholar]
  17. Khromykh A. A., Sedlak P. L., Guyatt K. J., Hall R. A., Westaway E. G. 1999; Efficient trans-complementation of the flavivirus kunjin NS5 protein but not of the NS1 protein requires its coexpression with other components of the viral replicase. J Virol 73:10272–10280[PubMed]
    [Google Scholar]
  18. Le Flohic G., Porphyre V., Barbazan P., Gonzalez J. P. 2013; Review of climate, landscape, and viral genetics as drivers of the Japanese encephalitis virus ecology. PLoS Negl Trop Dis 7:e2208 [View Article][PubMed]
    [Google Scholar]
  19. Li Z., Wang Y., Li X., Li X., Cao H., Zheng S. J. 2013; Critical roles of glucocorticoid-induced leucine zipper in infectious bursal disease virus (IBDV)-induced suppression of type I Interferon expression and enhancement of IBDV growth in host cells via interaction with VP4. J Virol 87:1221–1231 [View Article][PubMed]
    [Google Scholar]
  20. Lin Y. L., Chen L. K., Liao C. L., Yeh C. T., Ma S. H., Chen J. L., Huang Y. L., Chen S. S., Chiang H. Y. 1998; DNA immunization with Japanese encephalitis virus nonstructural protein NS1 elicits protective immunity in mice. J Virol 72:191–200[PubMed]
    [Google Scholar]
  21. Lindenbach B. D., Rice C. M. 1997; trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol 71:9608–9617[PubMed]
    [Google Scholar]
  22. Lindenbach B. D., Rice C. M. 1999; Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J Virol 73:4611–4621[PubMed]
    [Google Scholar]
  23. MacKenzie J. M., Jones M. K., Young P. R. 1996; Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology 220:232–240 [View Article][PubMed]
    [Google Scholar]
  24. Mason P. W. 1989; Maturation of Japanese encephalitis virus glycoproteins produced by infected mammalian and mosquito cells. Virology 169:354–364 [View Article][PubMed]
    [Google Scholar]
  25. Matsufuji S., Matsufuji T., Wills N. M., Gesteland R. F., Atkins J. F. 1996; Reading two bases twice: mammalian antizyme frameshifting in yeast. EMBO J 15:1360–1370[PubMed]
    [Google Scholar]
  26. Melian E. B., Hinzman E., Nagasaki T., Firth A. E., Wills N. M., Nouwens A. S., Blitvich B. J., Leung J., Funk A.other authors 2010; NS1′ of flaviviruses in the Japanese encephalitis virus serogroup is a product of ribosomal frameshifting and plays a role in viral neuroinvasiveness. J Virol 84:1641–1647 [View Article][PubMed]
    [Google Scholar]
  27. Morita K., Tadano M., Nakaji S., Kosai K., Mathenge E. G., Pandey B. D., Hasebe F., Inoue S., Igarashi A. 2001; Locus of a virus neutralization epitope on the Japanese encephalitis virus envelope protein determined by use of long PCR-based region-specific random mutagenesis. Virology 287:417–426 [View Article][PubMed]
    [Google Scholar]
  28. Muylaert I. R., Chambers T. J., Galler R., Rice C. M. 1996; Mutagenesis of the N-linked glycosylation sites of the yellow fever virus NS1 protein: effects on virus replication and mouse neurovirulence. Virology 222:159–168 [View Article][PubMed]
    [Google Scholar]
  29. Okamoto K., Kinoshita H., Parquet M. C., Raekiansyah M., Kimura D., Yui K., Islam M. A., Hasebe F., Morita K. 2012; Dengue virus strain DEN2 16681 utilizes a specific glycochain of syndecan-2 proteoglycan as a receptor. J Gen Virol 93:761–770 [View Article][PubMed]
    [Google Scholar]
  30. Osorio J. E., Ciuoderis K. A., Lopera J. G., Piedrahita L. D., Murphy D., Levasseur J., Carrillo L., Ocampo M. C., Hofmeister E. 2012; Characterization of West Nile viruses isolated from captive American Flamingoes (Phoenicopterus ruber) in Medellin, Colombia. Am J Trop Med Hyg 87:565–572 [View Article][PubMed]
    [Google Scholar]
  31. Plant E. P., Dinman J. D. 2006; Comparative study of the effects of heptameric slippery site composition on −1 frameshifting among different eukaryotic systems. RNA 12:666–673 [View Article][PubMed]
    [Google Scholar]
  32. Schlesinger J. J. 2006; Flavivirus nonstructural protein NS1: complementary surprises. Proc Natl Acad Sci U S A 103:18879–18880 [View Article][PubMed]
    [Google Scholar]
  33. Schneider C. A., Rasband W. S., Eliceiri K. W. 2012; NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675 [View Article][PubMed]
    [Google Scholar]
  34. Solomon T. 2004; Flavivirus encephalitis. N Engl J Med 351:370–378 [View Article][PubMed]
    [Google Scholar]
  35. Sumiyoshi H., Mori C., Fuke I., Morita K., Kuhara S., Kondou J., Kikuchi Y., Nagamatu H., Igarashi A. 1987; Complete nucleotide sequence of the Japanese encephalitis virus genome RNA. Virology 161:497–510 [View Article][PubMed]
    [Google Scholar]
  36. Sumiyoshi H., Hoke C. H., Trent D. W. 1992; Infectious Japanese encephalitis virus RNA can be synthesized from in vitro-ligated cDNA templates. J Virol 66:5425–5431[PubMed]
    [Google Scholar]
  37. van den Hurk A. F., Ritchie S. A., MacKenzie J. S. 2009; Ecology and geographical expansion of Japanese encephalitis virus. Annu Rev Entomol 54:17–35 [View Article][PubMed]
    [Google Scholar]
  38. Westaway E. G., Brinton M. A., Gaidamovich S. Ya, Horzinek M. C., Igarashi A., Kääriäinen L., Lvov D. K., Porterfield J. S., Russell P. K., Trent D. W. 1985; Flaviviridae . Intervirology 24:183–192 [View Article][PubMed]
    [Google Scholar]
  39. Wilson J. R., de Sessions P. F., Leon M. A., Scholle F. 2008; West Nile virus nonstructural protein 1 inhibits TLR3 signal transduction. J Virol 82:8262–8271 [View Article][PubMed]
    [Google Scholar]
  40. Winkelmann E. R., Widman D. G., Suzuki R., Mason P. W. 2011; Analyses of mutations selected by passaging a chimeric flavivirus identify mutations that alter infectivity and reveal an interaction between the structural proteins and the nonstructural glycoprotein NS1. Virology 421:96–104 [View Article][PubMed]
    [Google Scholar]
  41. Xia H., Zhao J., Li Y., Yin S., Tang S., Zhang Z., Yu J., Kou Z., Fan Z., Li T. 2013; Infection and propagation of Crimean-Congo hemorrhagic fever virus in embryonated chicken eggs. Virus Res 173:344–349 [View Article][PubMed]
    [Google Scholar]
  42. Ye Q., Li X. F., Zhao H., Li S. H., Deng Y. Q., Cao R. Y., Song K. Y., Wang H. J., Hua R. H.other authors 2012; A single nucleotide mutation in NS2A of Japanese encephalitis-live vaccine virus (SA14-14-2) ablates NS1′ formation and contributes to attenuation. J Gen Virol 93:1959–1964 [View Article][PubMed]
    [Google Scholar]
  43. Youn S., Li T., McCune B. T., Edeling M. A., Fremont D. H., Cristea I. M., Diamond M. S. 2012; Evidence for a genetic and physical interaction between nonstructural proteins NS1 and NS4B that modulates replication of West Nile virus. J Virol 86:7360–7371 [View Article][PubMed]
    [Google Scholar]
  44. Young L. B., Melian E. B., Khromykh A. A. 2013; NS1′ colocalizes with NS1 and can substitute for NS1 in West Nile virus replication. J Virol 87:9384–9390 [View Article][PubMed]
    [Google Scholar]
  45. Yu F., Le M. Q., Inoue S., Thai H. T., Hasebe F., Del Carmen Parquet M., Morita K. 2005; Evaluation of inapparent nosocomial severe acute respiratory syndrome coronavirus infection in Vietnam by use of highly specific recombinant truncated nucleocapsid protein-based enzyme-linked immunosorbent assay. Clin Diagn Lab Immunol 12:848–854[PubMed]
    [Google Scholar]
  46. Yu F., Hasebe F., Inoue S., Mathenge E. G., Morita K. 2007a; Identification and characterization of RNA-dependent RNA polymerase activity in recombinant Japanese encephalitis virus NS5 protein. Arch Virol 152:1859–1869 [View Article][PubMed]
    [Google Scholar]
  47. Yu F., Le M. Q., Inoue S., Hasebe F., Parquet M. C., Morikawa S., Morita K. 2007b; Recombinant truncated nucleocapsid protein as antigen in a novel immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of severe acute respiratory syndrome coronavirus infection. Clin Vaccine Immunol 14:146–149 [View Article][PubMed]
    [Google Scholar]
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