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Journal of Virology, February 2005, p. 1343-1350, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1343-1350.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

West Nile Virus Inhibits the Signal Transduction Pathway of Alpha Interferon

Ju-Tao Guo, Junpei Hayashi, and Christoph Seeger*

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Received 4 August 2004/ Accepted 3 September 2004

West Nile virus (WNV) is a human pathogen that can cause neurological disorders, including meningoencephalitis. Experiments with mice and mammalian cell cultures revealed that WNV exhibited resistance to the innate immune program induced by alpha interferon (IFN-{alpha}). We have investigated the nature of this inhibition and have found that WNV replication inhibited the activation of many known IFN-inducible genes, because it prevented the phosphorylation and activation of the Janus kinases JAK1 and Tyk2. As a consequence, activation of the transcription factors STAT1 and STAT2 did not occur in WNV-infected cells. Moreover, we demonstrated that the viral nonstructural proteins are responsible for this effect. Thus, our results provided an explanation for the observed resistance of WNV to IFN-{alpha} in cells of vertebrate origin.

* Corresponding author. Mailing address: Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111. Phone: (215) 728-4312. Fax: (215) 728-4329. E-mail: seeger{at}fccc.edu.

Journal of Virology, February 2005, p. 1343-1350, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1343-1350.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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