The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses.
The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses.
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PA-X 对 2009 年大流行 H1N1 和高致病性 H5N1 禽流感病毒毒力的贡献
DOI：
10.1038/srep08262
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发表时间：
2015-02-05
影响因子：
4.6
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Gao H;Sun Y;Hu J;Qi L;Wang J;Xiong X;Wang Y;He Q;Lin Y;Kong W;Seng LG;Sun H;Pu J;Chang KC;Liu X;Liu J
PA- x是一种由PA mRNA编码的新型蛋白，可降低1918年H1N1大流行病毒对小鼠的致病性。然而，PA-X蛋白在当前流行病学上重要的甲型流感病毒株中的重要性尚不清楚。在这项研究中，我们报告了PA-X缺陷的2009大流行性H1N1 （pH1N1）和高致病性H5N1禽流感病毒的致病性和病理效应。我们发现PA-X在pH1N1和H5N1病毒中的表达缺失增加了A549细胞中的病毒复制和凋亡，并增加了小鼠的毒力和宿主炎症反应。此外，PA- x缺陷的pH1N1和H5N1病毒上调了PA mRNA和蛋白的合成，并增加了病毒聚合酶的活性。PA- x的缺失还伴随着PA蛋白的核积累加速和PA对非病毒蛋白表达的抑制减弱。我们的研究强调了PA-X在调节病毒发病机制和致病性方面的作用。
PA-X is a novel protein encoded by PA mRNA and is found to decrease the pathogenicity of pandemic 1918 H1N1 virus in mice. However, the importance of PA-X proteins in current epidemiologically important influenza A virus strains is not known. In this study, we report on the pathogenicity and pathological effects of PA-X deficient 2009 pandemic H1N1 (pH1N1) and highly pathogenic avian influenza H5N1 viruses. We found that loss of PA-X expression in pH1N1 and H5N1 viruses increased viral replication and apoptosis in A549 cells and increased virulence and host inflammatory response in mice. In addition, PA-X deficient pH1N1 and H5N1 viruses up-regulated PA mRNA and protein synthesis and increased viral polymerase activity. Loss of PA-X was also accompanied by accelerated nuclear accumulation of PA protein and reduced suppression of PA on non-viral protein expression. Our study highlights the effects of PA-X on the moderation of viral pathogenesis and pathogenicity.
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4.8
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Lam WY;Yeung AC;Chu IM;Chan PK
通讯作者：
Chan PK
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PALESE, P
通讯作者：
PALESE, P
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