PB2蛋白T271A突变增强了欧亚类禽猪流感病毒在小鼠中的致病力  

Substitution T271A in PB2 Protein Enhances the Infectivity and Pathogenicity of Eurasian Avian⁃Like H1N1 Swine Influenza Virus in Mice

作　　者：冯兆民[1] 朱闻斐[1] 周丽娟 李希妍[1] 刘佳 高荣保[1] 王大燕[1] 舒跃龙[1,2] FENG Zhaomin;ZHU Wenfei;ZHOU Lijuan;LI Xiyan;LIU Jia;GAO Rongbao;WANG Dayan;SHU Yuelong(World Health Organization Global Influenza Collaboration Center for Reference and Research,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases,Key Laboratory for Medical Virology,National Health Commission,Beijing102206,China;School of Public Health(Shenzhen),Sun Yat-sen University,Guangdong 510006,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所,世界卫生组织全球流感参比和研究合作中心,感染性疾病诊治协同创新中心,国家卫生健康委员会医学病毒和病毒病重点实验室,北京102206 [2]中山大学公共卫生学院(深圳),广州510006

出　　处：《病毒学报》2020年第4期600-609,共10页Chinese Journal of Virology

基　　金：国家自然科学基金(项目号:81961128002),题目:基于生态大数据的中国禽流感病毒进化多样性和传播动力学预测预警研究;国家自然科学基金(项目号:81971941),题目:乙型流感病毒致病分子机制研究。

摘　　要：目前,欧亚类禽猪流感病毒(Eurasian avian-like H1N1 swine influenza viruses,EA H1N1 SIVs)在我国猪群中广泛流行,同时可跨越种属屏障感染人。PB2-T271A是H5N1、H7N9和2009年甲型H1N1流感病毒中关键的分子标记,可增加病毒在小鼠中的致病力。但是,PB2-T271A对EA H1N1 SIVs的影响尚不清楚。在本研究中,我们分析了PB2-T271A突变对EA H1N1 SIVs在细胞和小鼠中复制能力的影响。本研究发现,PB2-T271A突变增加了EA H1N1 SIVs在哺乳动物细胞和禽细胞中的复制能力,增加了EA H1N1 SIVs在小鼠中的致病力。此外,PB2-T271A突变增加了EA H1N1 SIVs的聚合酶活性。因此,我们应该加强对EA H1N1 SIVs中PB2-T271A位点的监测。Eurasian avian-like H1N1(EA H1N1)swine influenza viruses are widely prevalent in pigs in China,with sporadic human cases reported as well.Although it was one of the key molecular markers detected in avian H5N1 and H7N9 viruses and pandemic H1N12009 virus,the contribution of T271A in PB2 protein to EA H1N1 viruses is still unknown.In this study,we investigated the effects of mutation of residue 271 in PB2 protein on the viral properties of an EA H1N1 virus.The substitution PB2–T271A increased viral replication in mammalian and avian cell lines and enhanced viral polymerase activity in mammalian cells.The mutation enhanced viral infectivity,virulence,and pathogenicity in mice.Therefore,the T271A mutation in PB2 protein should be continually monitored in influenza viruses circulating in pigs and humans.

关 键 词：欧亚类禽猪流感病毒 PB2-T271A 复制 致病力 

分 类 号：R373[医药卫生—病原生物学]