Kubota Toru, Yokosawa Noriko, Yokota Shin-Ichi, Fujii Nobuhiro, Tashiro Masato, Kato Atsushi
Department of Virology III, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo 208-0011, Japan.
J Virol. 2005 Apr;79(7):4451-9. doi: 10.1128/JVI.79.7.4451-4459.2005.
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.
腮腺炎病毒（MuV）已被证明可通过利用病毒V蛋白，经蛋白酶体介导使信号转导和转录激活因子1（STAT1）完全降解，从而拮抗干扰素（IFN）的抗病毒作用（T. Kubota等人，《生物化学与生物物理研究通讯》283:255 - 259，2001年）。然而，我们发现MuV在感染细胞中细胞STAT1完全降解之前很久，就能抑制IFN信号传导以及随后抗病毒状态的产生。在MuV感染的细胞中，IFN-β分别使STAT1和STAT2酪氨酸残基（Y）在701和689位的核转位和磷酸化受到显著抑制，但Jak1和Tyk2的磷酸化未受抑制。瞬时表达的MuV V蛋白也抑制IFN-β诱导的Y701 - STAT1和Y689 - STAT2磷酸化，这表明V蛋白可在无需其他病毒成分帮助的情况下阻断IFN-β诱导的信号转导。最后，在已知对STAT1降解和抗IFN信号传导抑制所必需的C末端V独特区域，用丙氨酸残基取代半胱氨酸残基，导致V蛋白丧失抑制Y701 - STAT1和Y689 - STAT2磷酸化的功能。
