Mumps virus V protein antagonizes interferon without the complete degradation of STAT1.
Mumps virus (MuV) has been shown to antagonize the antiviral effects of interferon (IFN) through proteasome-mediated complete degradation of STAT1 by using the viral V protein (T. Kubota et al., Biochem. Biophys. Res. Commun. 283:255-259, 2001). However, we found that MuV could inhibit IFN signaling and the generation of a subsequent antiviral state long before the complete degradation of cellular STAT1 in infected cells. In MuV-infected cells, nuclear translocation and phosphorylation of STAT1 and STAT2 tyrosine residue (Y) at 701 and 689, respectively, by IFN-beta were significantly inhibited but the phosphorylation of Jak1 and Tyk2 was not inhibited. The transiently expressed MuV V protein also inhibited IFN-beta-induced Y701-STAT1 and Y689-STAT2 phosphorylation, suggesting that the V protein could block IFN-beta-induced signal transduction without the aid of other viral components. Finally, a substitution of an alanine residue in place of a cysteine residue in the C-terminal V-unique region known to be required for STAT1 degradation and inhibition of anti-IFN signaling resulted in the loss of V protein function to inhibit the Y701-STAT1 and Y689-STAT2 phosphorylation.
Kubota
Toru
T
Department of Virology III, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo 208-0011, Japan. kubota@nih.go.jp
Yokosawa
Noriko
N
Yokota
Shin-Ichi
S
Fujii
Nobuhiro
N
Tashiro
Masato
M
Kato
Atsushi
A
D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000882:Haplorhini; D016899:Interferon-beta / Q000037:antagonists & inhibitors*; D053613:Janus Kinase 1; D009109:Mumps virus / Q000472:pathogenicity*; D009154:Mutation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014764:Viral Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D014764:Viral Proteins; D016899:Interferon-beta; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1