Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon antagonist
Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon antagonist
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DOI：
10.1128/jvi.01634-06
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发表时间：
2007-03-01
影响因子：
5.4
通讯作者：
Hogue, Brenda G.
中科院分区：
文献类型：
--
作者：
Ye, Ye;Hauns, Kevin;Hogue, Brenda G.
最近出现的几种新型冠状病毒，包括严重急性呼吸道综合征的病因，显着增加了了解该病毒家族病毒与宿主细胞相互作用的重要性。我们使用小鼠肝炎病毒（MHV）A59作为模型，以深入了解冠状病毒如何影响I型α/β干扰素（IFN）系统。我们证明，MHV是耐I型干扰素。蛋白激酶R（PKR）和真核翻译起始因子的α亚基在感染细胞中不磷酸化。与2 '，5'-寡腺苷酸合成酶相关的RNase L活性不被激活或被阻断，因为细胞RNA不被降解。这些结果与感染后早期缺乏蛋白质翻译关闭一致。我们使用了一个完善的重组牛痘病毒（VV）为基础的表达系统，缺乏病毒IFN拮抗剂E3 L筛选病毒基因的能力，以挽救突变体的IFN敏感性。核衣壳（N）基因拯救VV Delta E3 L免于IFN敏感性。N基因表达防止细胞RNA降解，并部分挽救WW Delta E3 L病毒的戏剧性翻译关闭特征。然而，它不能阻止PKR磷酸化。结果表明，MHV N蛋白是一种I型IFN拮抗剂，可能在规避先天免疫应答中发挥作用。
The recent emergence of several new coronaviruses, including the etiological cause of severe acute respiratory syndrome, has significantly increased the importance of understanding virus-host cell interactions of this virus family. We used mouse hepatitis virus (MHV) A59 as a model to gain insight into how coronaviruses affect the type I alpha/beta interferon (IFN) system. We demonstrate that MHV is resistant to type I IFN. Protein kinase R (PKR) and the alpha subunit of eukaryotic translation initiation factor are not phosphorylated in infected cells. The RNase L activity associated with 2',5'-oligoadenylate synthetase is not activated or is blocked, since cellular RNA is not degraded. These results are consistent with lack of protein translation shutoff early following infection. We used a well-established recombinant vaccinia virus (VV)-based expression system that lacks the viral IFN antagonist E3L to screen viral genes for their ability to rescue the IFN sensitivity of the mutant. The nucleocapsid (N) gene rescued VV Delta E3L from IFN sensitivity. N gene expression prevents cellular RNA degradation and partially rescues the dramatic translation shutoff characteristic of the WW Delta E3L virus. However, it does not prevent PKR phosphorylation. The results indicate that the MHV N protein is a type I IFN antagonist that likely plays a role in circumventing the innate immune response.