Induction of Stress Granule-Like Structures in Vesicular Stomatitis Virus-Infected Cells
Induction of Stress Granule-Like Structures in Vesicular Stomatitis Virus-Infected Cells
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DOI：
10.1128/jvi.02305-12
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发表时间：
2013-01-01
影响因子：
5.4
通讯作者：
Pattnaik, Asit K.
中科院分区：
文献类型：
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作者：
Dinh, Phat X.;Beura, Lalit K.;Pattnaik, Asit K.
本实验室先前的研究显示，细胞聚（C）结合蛋白2（PCBP 2）下调水泡性口炎病毒（VSV）基因表达。我们在这里表明，VSV感染诱导细胞质中含有细胞RNA结合蛋白，包括PCBP 2，T细胞限制性细胞内抗原1（TIA 1）和TIA 1相关蛋白（TIAR）的颗粒状结构的形成。通过小干扰RNA（siRNA）而不是TIAR的消耗来消耗TIA 1，导致增强的VSV生长和基因表达。VSV诱导的颗粒似乎与热休克或氧化应激触发的细胞中产生的应激颗粒（SG）相似，但不包含一些真正的SG标记物，如真核起始因子3（eIF 3）或eIF 4A，或加工体（PB）标记物，如mRNA-脱帽酶1A（DCP 1a），因此可能不代表典型的SG或PB。我们的研究结果表明，VSV诱导的颗粒，这里称为SG样结构，含有病毒复制蛋白和RNA。SG样结构的形成和维持需要病毒复制和持续的蛋白质合成，但不需要完整的细胞骨架网络。这些结果表明，细胞对VSV感染的反应是通过聚集抗病毒蛋白，如PCBP 2和TIA 1，形成SG样结构。目前正在研究这些SG样结构在VSV感染细胞中的功能意义。
Previous studies from our laboratory revealed that cellular poly(C) binding protein 2 (PCBP2) downregulates vesicular stomatitis virus (VSV) gene expression. We show here that VSV infection induces the formation of granular structures in the cytoplasm containing cellular RNA-binding proteins, including PCBP2, T-cell-restricted intracellular antigen 1 (TIA1), and TIA1-related protein (TIAR). Depletion of TIA1 via small interfering RNAs (siRNAs), but not depletion of TIAR, results in enhanced VSV growth and gene expression. The VSV-induced granules appear to be similar to the stress granules (SGs) generated in cells triggered by heat shock or oxidative stress but do not contain some of the bona fide SG markers, such as eukaryotic initiation factor 3 (eIF3) or eIF4A, or the processing body (PB) markers, such as mRNA-decapping enzyme 1A (DCP1a), and thus may not represent canonical SGs or PBs. Our results revealed that the VSV- induced granules, called SG-like structures here, contain the viral replicative proteins and RNAs. The formation and maintenance of the SG-like structures required viral replication and ongoing protein synthesis, but an intact cytoskeletal network was not necessary. These results suggest that cells respond to VSV infection by aggregating the antiviral proteins, such as PCBP2 and TIA1, to form SG-like structures. The functional significance of these SG-like structures in VSV-infected cells is currently under investigation.