Differential effects of mutations in NS4B on West Nile virus replication and inhibition of interferon signaling.
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.
Evans
Jared D
JD
Fox Chase Cancer Center, Institute for Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111, USA. jared.evans@fccc.edu
Seeger
Christoph
C
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005786:Gene Expression Regulation; D006367:HeLa Cells / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D001618:beta-Lactamases / Q000378:metabolism
C080107:NS4B protein, flavivirus; D017361:Viral Nonstructural Proteins; D007372:Interferons; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human; D001618:beta-Lactamases
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