Phosphorylation of PB2 at serine 181 restricts viral replication and virulence of the highly pathogenic H5N1 avian influenza virus in mice

作     者：Jiao Hu Zixiong Zeng Xia Chen Manyu Zhang Zenglei Hu Min Gu Xiaoquan Wang Ruyi Gao Shunlin Hu Yu Chen Xiaowen Liu Daxin Peng Xiufan Liu 

作者机构：Animal Infectious Disease LaboratorySchool of Veterinary MedicineYangzhou UniversityYangzhou225009China Joint International Research Laboratory of Agriculture and Agri-Product SafetyThe Ministry of Education of ChinaYangzhou University225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and ZoonosisYangzhou UniversityYangzhou225009China Key Laboratory of Prevention and Control of Biological Hazard Factors(Animal Origin)for Agri-food Safety and QualityMinistry of Agriculture of China(26116120)Yangzhou UniversityYangzhou225009China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2024年第39卷第1期

页      面：97-112页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(32072832,32372976) by the National Key Research and Development Project of China(2021YFD1800202) by Jiangsu Province Agricultural Science&Technology Independent Innovation Funds[CX(21)3141] by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3553 and KYCX21_3277) by the Earmarked Fund for China Agriculture Research System(CARS-40) a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions 

主　　题：H5N1 influenza virus PB2 Phosphorylation Acetylation Viral fitness Mice 

摘      要：Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic *** modification of viral protein plays a substantial role in regulating IAV ***,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation ***,for the first time,we provide evidence that PB2 can also be acetylated at site ***,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based *** S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life *** analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein *** continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in ***,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory ***,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic ***,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.