Inhibition of cytoplasmic mRNA stress granule formation by a viral proteinase
Inhibition of cytoplasmic mRNA stress granule formation by a viral proteinase
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DOI：
10.1016/j.chom.2007.08.006
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发表时间：
2007-11-01
影响因子：
30.3
通讯作者：
Lloyd, Richard E.
中科院分区：
文献类型：
--
作者：
White, James P.;Cardenas, Ana Maria;Lloyd, Richard E.
哺乳动物细胞形成动态的细胞质mRNA应激颗粒(SGS)，以响应包括病毒感染在内的环境应激。SGs参与调节宿主mRNA的功能和代谢，但它们在病毒感染过程中的确切作用尚不清楚。SGS被认为是根据RNA结合蛋白TIA-1/TIAR或RAS-GAP SH3结构域结合蛋白(G3BP)的功能组装的。在这里，我们研究了一种典型的正链RNA病毒与SGS之间的关系。在脊髓灰质炎病毒感染的早期，SG的形成被诱导，但随着感染的进行，这种能力丧失，SGS分散。感染导致G3BP被脊髓灰质炎病毒3C酶切割，而不是TIA-1或TIAR。在脊髓灰质炎病毒感染期间，表达抗切割的G3BP可以恢复SG的形成，并显著抑制病毒复制。这些结果阐明了病毒干扰mRNP代谢和基因调控的机制，并支持G3BP在SG形成和限制病毒复制中的关键作用。
Mammalian cells form dynamic cytoplasmic mRNA stress granules (SGs) in response to environmental stresses including viral infections. SGs are involved in regulating host mRNA function and metabolism, although their precise role during viral infection is unknown. SGs are thought to assemble based on functions of the RNA-binding proteins TIA-1/TIAR or Ras-GAP SH3 domain-binding protein (G3BP). Here, we investigated the relationship between a prototypical plus-strand RNA virus and SGs. Early during poliovirus infection, SG formation is induced, but as infection proceeds this ability is lost, and SGs disperse. Infection resulted in cleavage of G3BP, but not TIA-1 or TIAR, by poliovirus 3C proteinase. Expression of a cleavage-resistant G3BP restored SG formation during poliovirus infection and significantly inhibited virus replication. These results elucidate a mechanism for viral interference with mRNP metabolism and gene regulation and support a critical role of G3BP in SG formation and restriction of virus replication.