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