West Nile virus inhibits the signal transduction pathway of alpha interferon.
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.
Guo
Ju-Tao
JT
Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111, USA.
Hayashi
Junpei
J
Seeger
Christoph
C
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D053613:Janus Kinase 1; D020411:Oligonucleotide Array Sequence Analysis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D053634:TYK2 Kinase; D014709:Vero Cells; D014779:Virus Replication; D014902:West Nile virus / Q000472:pathogenicity* / Q000502:physiology
D016898:Interferon-alpha; D011506:Proteins; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human