Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation
Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation
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DOI：
10.1073/pnas.0603144103
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发表时间：
2006-08-22
影响因子：
11.1
通讯作者：
Makino, Shinji
中科院分区：
文献类型：
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作者：
Kamitani, Wataru;Narayanan, Krishna;Makino, Shinji
严重急性呼吸综合征 (SARS) 冠状病毒 (SCoV) 会导致最近出现的一种与肺炎相关的人类疾病。单链正义病毒基因组RNA（基因1）的5'端三分之二编码16种成熟蛋白。 nsp1（基因 1 的最 N 端蛋白）的表达可阻止仙台病毒诱导的内源 IFN-β mRNA 积累，但不会抑制 IFN 调节因子 3（一种对于激活 IFN-β 启动子至关重要的蛋白质）的成熟化。此外，nsp1 的表达促进了表达的 RNA 转录本和宿主内源 mRNA 的降解，导致宿主蛋白质合成的强烈抑制。 SCoV 复制还促进了表达的 RNA 转录本和宿主 mRNA 的降解，表明 nsp1 在感染细胞中发挥了其 mRNA 不稳定功能。与 nsp1 诱导的 mRNA 不稳定相反，在表达 nsp1 的细胞或感染 SCoV 的细胞中，28S 和 18S rRNA 均未发生降解。这些数据表明，在受感染的细胞中，nsp1 促进宿主 mRNA 降解，从而抑制宿主基因表达，包括参与宿主先天免疫功能的蛋白质。 SCoV nsp1 介导的宿主 mRNA 降解促进可能在 SCoV 发病机制中发挥重要作用。
Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently emerged human disease associated with pneumonia. The 5' end two-thirds of the single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-beta mRNA accumulation without inhibiting climerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-beta promoter. Furthermore, nsp1 expression promoted degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a strong host protein synthesis inhibition. SCoV replication also promoted degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1 exerted its mRNA destabilization function in infected cells. In contrast to nsp1-induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in either nsp1-expressing cells or SCoV-infected cells. These data suggested that, in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses host gene expression, including proteins involved in host innate immune functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an important role in SCoV pathogenesis.