NS1 效应结构域二聚化对甲型流感病毒复制和毒力的贡献。
Contribution of NS1 effector domain dimerization to influenza A virus replication and virulence.
机构信息
Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
出版信息
J Virol. 2012 Dec;86(23):13095-8. doi: 10.1128/JVI.02237-12. Epub 2012 Sep 19.
Abstract
Conserved tryptophan-187 facilitates homodimerization of the influenza A virus NS1 protein effector domain. We generated a mutant influenza virus strain expressing NS1-W187R to destabilize this self-interaction. NS1-W187R protein exhibited lower double-stranded RNA (dsRNA)-binding activity, showed a temporal redistribution during infection, and was minimally compromised for interferon antagonism. The mutant virus replicated similarly to the wild type in vitro, but it was slightly attenuated for replication in mice, causing notably reduced morbidity and mortality. These data suggest biological relevance for the W187-mediated homotypic interaction of NS1.
摘要
保守的色氨酸 187 有助于流感 A 病毒 NS1 蛋白效应结构域的同源二聚化。我们生成了一株表达 NS1-W187R 的突变流感病毒株，以破坏这种自我相互作用。NS1-W187R 蛋白表现出较低的双链 RNA（dsRNA）结合活性，在感染过程中表现出时间上的重新分布，并且干扰素拮抗作用受到的影响最小。突变病毒在体外的复制与野生型相似，但在小鼠体内的复制能力略有减弱，导致发病率和死亡率明显降低。这些数据表明 NS1 的 W187 介导的同型相互作用具有生物学相关性。
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