Gao Zhao, Hu Jiao, Liang Yanyan, Yang Qian, Yan Kun, Liu Dong, Wang Xiaoquan, Gu Min, Liu Xiaowen, Hu Shunlin, Hu Zenglei, Liu Huimou, Liu Wenbo, Chen Sujuan, Peng Daxin, Jiao Xin-An, Liu Xiufan
Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou UniversityYangzhou, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Jiangsu Key Laboratory of Zoonosis, Yangzhou UniversityYangzhou, China.
Front Microbiol. 2017 Apr 28;8:739. doi: 10.3389/fmicb.2017.00739. eCollection 2017.
Accumulating data have identified the important roles of PA protein in replication and pathogenicity of influenza A virus (IAV). Identification of host factors that interact with the PA protein may accelerate our understanding of IAV pathogenesis. In this study, using immunoprecipitation assay combined with liquid chromatography-tandem mass spectrometry, we identified 278 human cellular proteins that might interact with PA of H5N1 IAV. Gene Ontology annotation revealed that the identified proteins are highly associated with viral translation and replication. Further KEGG pathway analysis of the interactome profile highlighted cellular pathways associated with translation, infectious disease, and signal transduction. In addition, Diseases and Functions analysis suggested that these cellular proteins are highly related with Organismal Injury and Abnormalities and Cell Death and Survival. Moreover, two cellular proteins (nucleolin and eukaryotic translation elongation factor 1-alpha 1) identified both in this study and others were further validated to interact with PA using co-immunoprecipitation and co-localization assays. Therefore, this study presented the interactome data of H5N1 IAV PA protein in human cells which may provide novel cellular target proteins for elucidating the potential molecular functions of PA in regulating the lifecycle of IAV in human cells.
越来越多的数据表明，PA蛋白在甲型流感病毒（IAV）的复制和致病性中发挥着重要作用。鉴定与PA蛋白相互作用的宿主因子可能会加速我们对IAV发病机制的理解。在本研究中，我们采用免疫沉淀分析结合液相色谱-串联质谱法，鉴定出278种可能与H5N1 IAV的PA相互作用的人类细胞蛋白。基因本体注释显示，所鉴定的蛋白与病毒翻译和复制高度相关。对相互作用组图谱的进一步KEGG通路分析突出了与翻译、传染病和信号转导相关的细胞通路。此外，疾病和功能分析表明，这些细胞蛋白与机体损伤和异常以及细胞死亡和存活高度相关。此外，在本研究和其他研究中均鉴定出的两种细胞蛋白（核仁素和真核翻译延伸因子1-α1），通过免疫共沉淀和共定位分析进一步验证了它们与PA的相互作用。因此，本研究展示了H5N1 IAV PA蛋白在人类细胞中的相互作用组数据，这可能为阐明PA在调节IAV在人类细胞中的生命周期中的潜在分子功能提供新的细胞靶蛋白。
