The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation
The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation
复制标题
猿猴病毒 5 的 V 蛋白通过靶向 STAT1 进行蛋白酶体介导的降解来抑制干扰素信号传导
DOI：
10.1128/jvi.73.12.9928-9933.1999
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发表时间：
1999-12-01
影响因子：
5.4
通讯作者：
Randall, RE
中科院分区：
文献类型：
--
作者：
Didcock, L;Young, DF;Randall, RE
要在体内复制，病毒必须规避细胞抗病毒机制，包括干扰素诱导的抗病毒机制（IFN）。在这里，我们证明猿猴病毒5（SV5）通过抑制IFN刺激的基因因子3的形成和γ激活的因子转录复合物来阻止人类IFN信号传导，这些因子与激活IFN-Alpha/beta/beta-和IFN-Gamma有关 - 反应基因。 SV5通过特异性靶向SV5（两种转录复合物共有的一个成分）来抑制这些复合物的形成，以促进蛋白酶体介导的降解。在没有其他病毒蛋白的情况下，SV5结构蛋白V的表达也抑制了IFN信号传导并诱导STAT1的降解。在感染SV5后，在没有病毒蛋白合成的情况下，STAT1降解，并且在感染后长达4天仍无法检测到，此外，即使细胞处于抗病毒状态，STAT1也被降解在IFN预处理的细胞中。由于对艾滋病毒的细胞进行预处理延迟，但不能阻止病毒复制和蛋白质合成，因此这些观察结果表明，在感染IFN预处理细胞后，SV5在细胞内保持可行，直到它们最终脱离抗病毒状态。
To replicate in vivo, viruses must circumvent cellular antiviral defense mechanisms, including those induced by the interferons (IFNs). Here we demonstrate that simian virus 5 (SV5) blocks IFN signalling in human tells by inhibiting the formation of the IFN-stimulated gene factor 3 and gamma-activated factor transcription complexes that are involved in activating IFN-alpha/beta- and IFN-gamma-responsive genes, respectively. SV5 inhibits the formation of these complexes by specifically targeting SV5, a component common to both transcription complexes, for proteasome-mediated degradation. Expression of the SV5 structural protein V, in the absence of other virus proteins, also inhibited IFN signalling and induced the degradation of STAT1. Following infection with SV5, STAT1 was degraded in the absence of virus protein synthesis and remained undetectable for up to 4 days postinfection, Furthermore, STAT1 was also degraded in IFN-pretreated cells, even though the cells were in an antiviral state. Since pretreatment of cells with HIV delayed but did not prevent virus replication and protein synthesis, these observations suggest that following infection of IFN-pretreated cells, SV5 remains viable within the cells until they eventually go out of the antiviral state.