Differential effects of mutations in NS4B on West Nile virus replication and inhibition of interferon signaling

Jared D. Evans, Christoph Seeger

Research output: Contribution to journalArticle

Abstract

West Nile virus (WNV) is a human pathogen that can cause symptomatic infections associated with meningitis and encephalitis. Previously, we demonstrated that replication of WNV inhibits the interferon (IFN) signal transduction pathway by preventing the accumulation of phosphorylated Janus kinase 1 (JAK1) and tyrosine kinase 2 (Tyk2) (J. T. Guo et al., J. Virol. 79:1343-1350, 2005). Through a genetic analysis, we have now identified a determinant on the nonstructural protein 4B (NS4B) that controls IFN resistance in HeLa cells expressing subgenomic WNV replicons lacking the structural genes. However, in the context of infectious genomes, the same determinant did not influence IFN signaling. Thus, our results indicate that NS4B may be sufficient to inhibit the IFN response in replicon cells and suggest a role for structural genes, or as yet unknown interactions, in the inhibition of the IFN signaling pathway during WNV infections.

Original languageEnglish (US)
Pages (from-to)11809-11816
Number of pages8
JournalJournal of Virology
Volume81
Issue number21
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

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West Nile virus
interferons
Virus Replication
virus replication
Interferons
mutation
Mutation
replicon
Replicon
structural genes
Proteins
proteins
Janus Kinase 1
non-specific protein-tyrosine kinase
TYK2 Kinase
meningitis
Virus Diseases
Encephalitis
encephalitis
HeLa Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Differential effects of mutations in NS4B on West Nile virus replication and inhibition of interferon signaling. / Evans, Jared D.; Seeger, Christoph.

In: Journal of Virology, Vol. 81, No. 21, 01.11.2007, p. 11809-11816.

Research output: Contribution to journalArticle

Evans, Jared D. ; Seeger, Christoph. / Differential effects of mutations in NS4B on West Nile virus replication and inhibition of interferon signaling. In: Journal of Virology. 2007 ; Vol. 81, No. 21. pp. 11809-11816.
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