Host Interaction Analysis of PA-N155 and PA-N182 in Chicken Cells Reveals an Essential Role of UBA52 for Replication of H5N1 Avian Influenza Virus.
Host Interaction Analysis of PA-N155 and PA-N182 in Chicken Cells Reveals an Essential Role of UBA52 for Replication of H5N1 Avian Influenza Virus.
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鸡细胞中 PA-N155 和 PA-N182 的宿主相互作用分析揭示了 UBA52 在 H5N1 禽流感病毒复制中的重要作用
DOI：
10.3389/fmicb.2018.00936
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发表时间：
2018
影响因子：
5.2
通讯作者：
Zhao G
中科院分区：
文献类型：
--
作者：
Wang Q;Li Q;Liu T;Chang G;Sun Z;Gao Z;Wang F;Zhou H;Liu R;Zheng M;Cui H;Chen G;Li H;Yuan X;Wen J;Peng D;Zhao G
PA-N155和PA-N182蛋白分别由H5 N1甲型流感病毒（IAV）RNA聚合酶酸性蛋白（PA）mRNA的第11和第13位起始密码子AUG翻译而来，在病毒复制中起重要作用。PA-N155和PA-N182与宿主蛋白之间的相互作用知之甚少。研究了H5 N1 IAV的PA-N155和PA-N182在鸡细胞中的相互作用，同时通过免疫沉淀捕获它们的相互作用复合物并通过质谱分析。共鉴定出491个（PA-N155）和302个（PA-N182）相互作用蛋白。基因本体和途径富集分析表明，两个相互作用体的蛋白质在RNA加工、病毒加工和蛋白质转运过程中富集，与蛋白酶体、核糖体和氨酰-tRNA生物合成信号通路相关的蛋白质显著富集，提示它们在H5 N1 IAV感染中可能发挥作用。PA，PA-N155和PA-N182的相互作用组的比较分析确定UBA 52作为与所有三种病毒蛋白相互作用的保守宿主因子。UBA 52是由N端的泛素和C端的核糖体蛋白L40组成的融合蛋白。UBA 52的敲低显著降低了鸡细胞中H5 N1 IAV的滴度，并伴随着促炎细胞因子的减弱产生。我们对流感病毒-宿主蛋白质相互作用组的分析确定UBA 52为病毒复制的PA相互作用蛋白。
PA-N155 and PA-N182 proteins were translated from the 11th and 13th start codon AUG of the RNA polymerase acidic protein (PA) mRNA of H5N1 influenza A virus (IAV), which plays an important role in viral replication. Little is known about the interactions between PA-N155 and PA-N182 and the host proteins. This study investigated the interaction landscape of PA-N155 and PA-N182 of H5N1 IAV in chicken cells while their interacting complexes were captured by immunoprecipitation and analyzed by mass spectrometry. A total of 491 (PA-N155) and 302 (PA-N182) interacting proteins were identified. Gene ontology and pathway enrichment analyses showed that proteins of the two interactomes were enriched in RNA processing, viral processing and protein transport, and proteins related to signaling pathways of proteasome, ribosome, and aminoacy1-tRNA biosynthesis were significantly enriched, suggesting their potential roles in H5N1 IAV infection. Comparative analysis of the interactome of PA, PA-N155, and PA-N182 identified UBA52 as a conserved host factor that interacted with all three viral proteins. UBA52 is a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein L40 at the C terminus. Knockdown of UBA52 significantly decreased the titer of H5N1 IAV in chicken cells and was accompanied with attenuated production of proinflammatory cytokines. Our analyses of the influenza–host protein interactomes identified UBA52 as a PA interaction protein for virus replication.
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影响因子：
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作者：
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影响因子：
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