PA 基因中的自然发生突变是导致大流行性 H1N1/09 流感病毒在小鼠中毒力增强的关键因素。
Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice.
机构信息
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
出版信息
J Virol. 2014 Apr;88(8):4600-4. doi: 10.1128/JVI.03158-13. Epub 2014 Feb 12.
Abstract
We examined the molecular basis of virulence of pandemic H1N1/09 influenza viruses by reverse genetics based on two H1N1/09 virus isolates (A/California/04/2009 [CA04] and A/swine/Shandong/731/2009 [SD731]) with contrasting pathogenicities in mice. We found that four amino acid mutations (P224S in the PA protein [PA-P224S], PB2-T588I, NA-V106I, and NS1-I123V) contributed to the lethal phenotype of SD731. In particular, the PA-P224S mutation when combined with PA-A70V in CA04 drastically reduced the virus's 50% mouse lethal dose (LD50), by almost 1,000-fold.
摘要
我们通过基于两个具有不同致病性的 H1N1/09 病毒分离株（A/加利福尼亚/04/2009 [CA04] 和 A/猪/山东/731/2009 [SD731]）的反向遗传学研究了大流行性 H1N1/09 流感病毒的毒力分子基础。我们发现四个氨基酸突变（PA 蛋白中的 P224S [PA-P224S]、PB2-T588I、NA-V106I 和 NS1-I123V）导致了 SD731 的致死表型。特别是，当 CA04 中的 PA-P224S 突变与 PA-A70V 结合时，病毒的半数致死量（LD50）几乎降低了 1000 倍。
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