PMID- 17715229 OWN - NLM STAT- MEDLINE DCOM- 20071127 LR - 20181113 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 81 IP - 21 DP - 2007 Nov TI - Differential effects of mutations in NS4B on West Nile virus replication and inhibition of interferon signaling. PG - 11809-16 AB - 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. FAU - Evans, Jared D AU - Evans JD AD - Fox Chase Cancer Center, Institute for Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111, USA. jared.evans@fccc.edu FAU - Seeger, Christoph AU - Seeger C LA - eng SI - GENBANK/EF536932 GR - T32 CA009035/CA/NCI NIH HHS/United States GR - T32 CA 09035-30/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070822 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (NS4B protein, flavivirus) RN - 0 (Viral Nonstructural Proteins) RN - 9008-11-1 (Interferons) RN - EC 2.7.10.2 (JAK1 protein, human) RN - EC 2.7.10.2 (Janus Kinase 1) RN - EC 2.7.10.2 (TYK2 Kinase) RN - EC 2.7.10.2 (TYK2 protein, human) RN - EC 3.5.2.6 (beta-Lactamases) SB - IM MH - Animals MH - Cell Line MH - Cricetinae MH - *Gene Expression Regulation MH - HeLa Cells/*virology MH - Humans MH - Interferons/*metabolism MH - Janus Kinase 1/*metabolism MH - Molecular Sequence Data MH - *Mutation MH - Phosphorylation MH - Signal Transduction MH - TYK2 Kinase/*metabolism MH - Viral Nonstructural Proteins/chemistry/*genetics MH - beta-Lactamases/metabolism PMC - PMC2168815 EDAT- 2007/08/24 09:00 MHDA- 2007/12/06 09:00 PMCR- 2008/03/01 CRDT- 2007/08/24 09:00 PHST- 2007/08/24 09:00 [pubmed] PHST- 2007/12/06 09:00 [medline] PHST- 2007/08/24 09:00 [entrez] PHST- 2008/03/01 00:00 [pmc-release] AID - JVI.00791-07 [pii] AID - 0791-07 [pii] AID - 10.1128/JVI.00791-07 [doi] PST - ppublish SO - J Virol. 2007 Nov;81(21):11809-16. doi: 10.1128/JVI.00791-07. Epub 2007 Aug 22.