PDF(Pubmed)
Abstract：
Influenza A virus can infect respiratory tracts and may cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to support viral replication and cause pathogenicity. The influenza viral PA protein is not only a subunit of influenza viral polymerase but also a virulence factor involved in pathogenicity during infection. To explore the role of the influenza virus PA protein in regulating host biological processes, we performed immunoprecipitation and LC‒MS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, and H3N2 viruses. The results demonstrated that proteins located in the mitochondrion, proteasome, and nucleus are associated with the PA protein. We further discovered that the PA protein is partly located in mitochondria by immunofluorescence and mitochondrial fractionation and that overexpression of the PA protein reduces mitochondrial respiration. In addition, our results revealed the interaction between PA and the mitochondrial matrix protein PYCR2 and the antiviral role of PYCR2 during influenza A virus replication. Moreover, we found that the PA protein could also trigger autophagy and disrupt mitochondrial homeostasis. Overall, our research revealed the impacts of the influenza A virus PA protein on mitochondrial function and autophagy.
摘要：
甲型流感病毒可以感染呼吸道，并可能导致人类严重疾病。由甲型流感病毒编码的蛋白质可以与细胞因子相互作用并失调宿主生物过程以支持病毒复制并引起致病性。流感病毒PA蛋白不仅是流感病毒聚合酶的一个亚单位,而且是在感染过程中与致病性有关的毒力因子。探讨流感病毒PA蛋白在调节宿主生物学过程中的作用,我们进行了免疫沉淀和LC-MS/MS,以在全球范围内鉴定与甲型H1N1流感,2009大流行H1N1和H3N2病毒PA蛋白相互作用的细胞因子.结果表明，位于线粒体中的蛋白质，蛋白酶体,和细胞核与PA蛋白相关。我们进一步发现，通过免疫荧光和线粒体分馏，PA蛋白部分位于线粒体中，并且PA蛋白的过表达减少了线粒体呼吸。此外,我们的结果揭示了PA与线粒体基质蛋白PYCR2之间的相互作用以及PYCR2在甲型流感病毒复制过程中的抗病毒作用.此外，我们发现PA蛋白还可以触发自噬并破坏线粒体稳态.总的来说,我们的研究揭示了甲型流感病毒PA蛋白对线粒体功能和自噬的影响.
