Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells

作     者：Hang Yang Huijun Yuan Xiaohui Zhao Meng Xun Shangrui Guo Nan Wang Bing Liu Hongliang Wang Hang Yang;Huijun Yuan;Xiaohui Zhao;Meng Xun;Shangrui Guo;Nan Wang;Bing Liu;Hongliang Wang

作者机构：Department of Pathogen Biology and ImmunologySchool of Basic Medical SciencesXi'an Jiaotong University Health Science CenterXi'an710061China School of PharmacyXi’an Jiaotong University Health Science CenterXi'an710061China BioBankThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of Life SciencesFaculty of Natural SciencesImperial College LondonLondonSW72AZUnited Kingdom Key Laboratory of Environment and Genes Related to DiseasesXi'an Jiaotong UniversityXi'an710061China 

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

年 卷 期：2022年第37卷第3期

页      面：380-389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(81871662,82150201) Xi’an Jiaotong University Fund(xzy012019066 and xzy032020037) Xi’an Jiaotong University Health Science Center-Qinnong Bank Fund(QNXJTU-04&QNXJTU-07)。 

主　　题：SARS-CoV-2 Endocytosis Phosphoinositides Angiotensin converting enzyme 2(ACE2) Syncytium 

摘      要：The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.