Sendai virus blocks alpha interferon signaling to signal transducers and activators of transcription.
We demonstrate here that Sendai virus (SeV) blocks alpha interferon (IFN-alpha) signaling to signal transducers and activators of transcription (STATs) in HeLa cells. IFN-alpha-stimulated tyrosine phosphorylation of STATs and subsequent formation of the IFN-stimulated gene factor 3 transcription complex were inhibited in SeV-infected cells, resulting in inefficient induction of IFN-stimulated gene products. None of the components of the signaling pathway-type I IFN receptor subunits Jak1, Tyk2, Stat1, Stat2, and p48-was degraded. Moreover, tyrosine phosphorylation of Jak1 in response to IFN-alpha was unaffected at the early phase of infection, suggesting that oligomerization of the receptor subunits proceeded normally. In contrast to Jak1, IFN-alpha-stimulated tyrosine phosphorylation of Tyk2 was partially inhibited. Therefore, this partial inhibition of activation of Tyk2 probably contributes to the subsequent failure in the activation of STATs.
Komatsu
T
T
Department of Microbiology, Fukui Medical University School of Medicine, Yoshida-gun, Fukui 910-1193, Japan. koma@fmsrsa.fukui-med.ac.jp
Takeuchi
K
K
Yokoo
J
J
Tanaka
Y
Y
Gotoh
B
B
D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D053613:Janus Kinase 1; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D018108:Respirovirus / Q000472:pathogenicity*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D008565:Membrane Proteins; D011506:Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; C097656:polypeptide 48; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human