Mutual antagonism of mouse-adaptation mutations in HA and PA proteins on H9N2 virus replication

作     者：Liping Ma Huabin Zheng Xianliang Ke Rui Gui Zhongzi Yao Jiasong Xiong Quanjiao Chen 

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.