Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts.

Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts.
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DOI:
10.1038/ncomms6021
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发表时间:
2014-10-07
影响因子:
16.6
通讯作者:
Kawaoka Y
Kawaoka Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Fan S;Hatta M;Kim JH;Halfmann P;Imai M;Macken CA;Le MQ;Nguyen T;Neumann G;Kawaoka Y

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高致病性H5 N1禽流感病毒零星传播给人类,造成高死亡率。适应的机制基础仍然知之甚少,尽管已知病毒蛋白PB 2中的几个残基对该事件很重要。在这里,我们证明了三个残基,147 T,339 T和588 T,在PB 2中发挥关键作用的禽H5 N1流感病毒在哺乳动物宿主中的毒力在体外和体内,并一起,导致在表型相媲美的先前已知的PB 2 - 627 K突变赋予的病毒聚合酶活性。从一个致命的人类病例中分离出的具有PB 2中的三个残基和627 K的病毒比仅具有PB 2中的三个残基或627 K的病毒更具致病性。重要的是,携带前三种PB 2残基的H5 N1病毒近年来在自然界的鸟类中广泛传播。
Highly pathogenic avian H5N1 influenza viruses have sporadically transmitted to humans causing high mortality. The mechanistic basis for adaptation is still poorly understood, although several residues in viral protein PB2 are known to be important for this event. Here we demonstrate that three residues, 147T, 339T and 588T, in PB2 play critical roles in the virulence of avian H5N1 influenza viruses in a mammalian host in vitro and in vivo and, together, result in a phenotype comparable to that conferred by the previously known PB2-627K mutation with respect to virus polymerase activity. A virus with the three residues and 627K in PB2, as has been isolated from a lethal human case, is more pathogenic than viruses with only the three residues or 627K in PB2. Importantly, H5N1 viruses bearing the former three PB2 residues have circulated widely in recent years in avian species in nature.
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