Transmembrane domain of IFITM3 is responsible for its interaction with influenza virus HA_(2) subunit

作     者：Wang Xu Yuhang Wang Letian Li Xiaoyun Qu Quan Liu Tiyuan Li Shipin Wu Ming Liao Ningyi Jin Shouwen Du Chang Li Wang Xu;Yuhang Wang;Letian Li;Xiaoyun Qu;Quan Liu;Tiyuan Li;Shipin Wu;Ming Liao;Ningyi Jin;Shouwen Du;Chang Li

作者机构：College of Veterinary MedicineNorthwest A&F UniversityYangling712100China Department of Infectious DiseasesThe Second Clinical Medical College of Jinan UniversityShenzhen518020China Research Unit of Key Technologies for Prevention and Control of Virus ZoonosesChinese Academy of Medical SciencesChangchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchun130122China Key Laboratory of Zoonosis of Ministry of AgricultureSouth China Agricultural UniversityGuangzhou510642China 

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

年 卷 期：2022年第37卷第5期

页      面：664-675页

核心收录：

学科分类：0710[理学-生物学] 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 (31702210, 31972719) the CAMS Innovation Fund for Medical Sciences (2020–12M-5-001) 

主　　题：Interferon-inducible transmembrane protein 3 (IFITM3) Influenza virus Hemagglutinin(HA) Interaction Transmembrane domain 

摘      要：Interferon-inducible transmembrane protein 3(IFITM3)inhibits influenza virus infection by blocking viral membrane fusion,but the exact mechanism remains elusive.Here,we investigated the function and key region of IFITM3 in blocking influenza virus entry mediated by hemagglutinin(HA).The restriction of IFITM3 on HAmediated viral entry was confirmed by pseudovirus harboring HA protein from H5 and H7 influenza viruses.Subcellular co-localization and immunocoprecipitation analyses revealed that IFITM3 partially co-located with the full-length HA protein and could directly interact with HA_(2) subunit but not HA_(1) subunit of H5 and H7 virus.Truncated analyses showed that the transmembrane domain of the IFITM3 and HA_(2) subunit might play an important role in their interaction.Finally,this interaction of IFITM3 was also verified with HA_(2) subunits from other subtypes of influenza A virus and influenza B virus.Overall,our data demonstrate for the first time a direct interaction between IFITM3 and influenza HA protein via the transmembrane domain,providing a new perspective for further exploring the biological significance of IFITM3 restriction on influenza virus infection or HA-mediated antagonism or escape.