Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and processing bodies
Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and processing bodies
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DOI：
10.1111/j.1462-5822.2007.00951.x
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
de Haan, Cornelis A. M.
中科院分区：
文献类型：
--
作者：
Raaben, Matthijs;Koerkamp, Marian J. A. Groot;de Haan, Cornelis A. M.
许多病毒，包括冠状病毒，诱导宿主翻译关闭，同时维持其自身基因产物的合成。在这项研究中，我们进行了全基因组微阵列分析的表达模式的小鼠肝炎冠状病毒（MHV）感染的细胞。在MHV诱导的宿主翻译关闭时，观察到许多mRNA的下调，其中许多mRNA编码蛋白质转录相关因子。这种下调，这是一个细胞应激反应，是依赖于病毒复制和mRNA衰变引起的。同时，在MHV感染的细胞中，真核翻译起始因子2 α的磷酸化增加。此外，还出现了应激颗粒和加工体，它们分别是mRNA停滞和降解的场所。我们建议，MHV复制诱导宿主翻译关闭通过触发一个集成的应激反应。然而，MHV复制本身似乎并不受益于宿主蛋白质合成的抑制，至少在体外，因为病毒复制没有受到负面影响，而是在翻译关闭受损的细胞中增强。
Many viruses, including coronaviruses, induce host translational shutoff, while maintaining synthesis of their own gene products. In this study we performed genome-wide microarray analyses of the expression patterns of mouse hepatitis coronavirus (MHV)-infected cells. At the time of MHV-induced host translational shutoff, downregulation of numerous mRNAs, many of which encode protein translation-related factors, was observed. This downregulation, which is reminiscent of a cellular stress response, was dependent on viral replication and caused by mRNA decay. Concomitantly, phosphorylation of the eukaryotic translation initiation factor 2 alpha was increased in MHV-infected cells. In addition, stress granules and processing bodies appeared, which are sites for mRNA stalling and degradation respectively. We propose that MHV replication induces host translational shutoff by triggering an integrated stress response. However, MHV replication per se does not appear to benefit from the inhibition of host protein synthesis, at least in vitro, since viral replication was not negatively affected but rather enhanced in cells with impaired translational shutoff.