2016年2月，《Journal of Proteomics》杂志上在线发表中国农业科学院北京畜牧兽医研究所赵桂苹研究员题为“Host Cell interactome of PA protein of H5N1 influenza A virus in chicken cells”最新研究成果，团队利用亲和纯化-质谱技术(AP-MS)对H5N1流感病毒聚合酶亚基PA在鸡细胞中的互作蛋白进行了分析鉴定，从生物化学和蛋白互作的角度探讨了流感病毒侵染宿主细胞和宿主防御病毒感染的可能机制。

流感病毒无法自主复制，必须依赖于宿主细胞系统方可完成病毒的复制和感染。蛋白-蛋白互作是流感病毒募集和雇佣宿主细胞因子参与自身复制的最重要的方式，此外宿主对病毒的防御也主要通过蛋白间互作实现。PA基因是流感病毒RNA聚合酶的重要成分，其核酸内切酶活性可切割宿主mRNA用于病毒基因组的合成。该研究利用AP-MS技术，鉴定得到134个和PA有相互作用的宿主蛋白。研究发现细胞内参与DNA复制的MCM复合物、参与内质网和细胞质间物质转运的COPI复合物及参与蛋白质降解的26S蛋白酶体等蛋白复合物和PA有着广泛的蛋白间相互作用。此外，该研究还发现了多个和PA有相互作用的候选宿主蛋白，如调控真核生物蛋白质折叠的CCT5、参与蛋白质转运的SEC61A1、影响mRNA脱去帽子结构的DDX6以及蛋白激酶CDK2等，相关PA-宿主蛋白互作的生物学功能正在深入研究中。

该研究揭示了和流感病毒密切关联的潜在的宿主促/抗流感因子，对家禽抗流感育种有重要的指导意义。

原文摘要：Influenza A virus (IAV) heavily depends on viral-host protein interactions in order to replicate and spread. Identification of host factors that interact with viral proteins plays crucial roles in understanding the mechanism of IAV infection. Here we report the interaction landscape of H5N1 IAV PA protein in chicken cells through the use of affinity purification and mass spectrometry. PA protein was expressed in chicken cells and PA interacting complexes were captured by co-immunoprecipitation and analyzed by mass spectrometry. A total of 134 proteins were identified as PA-host interacting factors. Protein complexes including the minichromosome maintenance complex (MCM), 26S proteasome and the coat protein I (COPI) complex associated with PA in chicken cells, indicating the essential roles of these functional protein complexes during the course of IAV infection. Gene Ontology and pathway enrichment analysis both showed strong enrichment of PA interacting proteins in the category of DNA replication, covering genes such as PCNA, MCM2, MCM3, MCM4, MCM5 and MCM7. This study has uncovered the comprehensive interactome of H5N1 IAV PA protein in its chicken host and helps to establish the foundation for further investigation into the newly identified viral-host interactions.