Mutual antagonism of mouse-adaptation mutations in HA and PA proteins on H9N2 virus replication
作者机构:CAS Key Laboratory of Special Pathogens and BiosafetyWuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Hubei Jiangxia LaboratoryWuhan430207China University of Chinese Academy of SciencesBeijing100049China
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:56-70页
核心收录:
学科分类:0710[理学-生物学] 090601[农学-基础兽医学] 09[农学] 0906[农学-兽医学]
基 金:supported by the National Key Research and Development Program of China(NKPs)(2022YFC2604101) the National Science and Technology Major Project of China(2020ZX10001016-002)
主 题:Influenza Avirus(IAV) H9N2 HA PA Antagonism Mouse adaptation
摘 要:Avian H9N2 viruses have wide host range among the influenza A ***,knowledge of H9N2 mammalian adaptation is *** explore the molecular basis of the adaptation to mammals,we performed serial lung passaging of the H9N2 strain A/chicken/Hunan/8.27 YYGK3W3-OC/2018(3W3)in mice and identified six mutations in the hemagglutinin(HA)and polymerase acidic(PA)*** L226Q,T511I,and A528V of HA were responsible for enhanced pathogenicity and viral replication in mice;notably,HA-L226Q was the key *** T97I,I545V,and S594G of PA contributed to enhanced polymerase activity in mammalian cells and increased viral replication levels in vitro and in ***-T97I increased viral polymerase activity by accelerating the viral polymerase complex *** findings revealed that the viral replication was affected by the presence of PA-97I and/or PA-545V in combination with a triple-point HA ***,the double-and triple-point PA mutations demonstrated antagonistic effect on viral replication when combined with ***,any combination of PA mutations,along with double-point HA mutations,resulted in antagonistic effect on viral *** also observed antagonism in viral replication between PA-545V and PA-97I,as well as between HA-528V and *** findings demonstrated that several antagonistic mutations in HA and PA proteins affect viral replication,which may contribute to the H9N2 virus adaptation to mice and mammalian *** findings can potentially contribute to the monitoring of H9N2 field strains for assessing their potential risk in mammals.