Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells

作     者：Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng Wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou Yuan Zhao Dexuan Kuang Junbin Wang Haixuan Wang Siyuan Chen Min Luo Ziqi Zhang Tiangi Lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei Wang Guobo Shen Guangwen Lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling Wang Jiong Li Xiangrong Song Lunzhi Dai Chong Chen Jia Geng Maling Gou Lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong Shuaiyao Lu Xiaozhong Peng Xiawei Wei Weiqi Hong;Jingyun Yang;Jun Zou;Zhenfei Bi;Cai He;Hong Lei;Xuemei He;Xue Li;Aqu Alu;Wenyan Ren;Zeng Wang;Xiaohua Jiang;Kunhong Zhong;Guowen Jia;Yun Yang;Wenhai Yu;Qing Huang;Mengli Yang;Yanan Zhou;Yuan Zhao;Dexuan Kuang;Junbin Wang;Haixuan Wang;Siyuan Chen;Min Luo;Ziqi Zhang;Tianqi Lu;Li Chen;Haiying Que;Zhiyao He;Qiu Sun;Wei Wang;Guobo Shen;Guangwen Lu;Zhiwei Zhao;Li Yang;Jinliang Yang;Zhenling Wang;Jiong Li;Xiangrong Song;Lunzhi Dai;Chong Chen;Jia Geng;Maling Gou;Lu Chen;Haohao Dong;Yong Peng;Canhua Huang;Zhiyong Qian;Wei Cheng;Changfa Fan;Yuquan Wei;Zhaoming Su;Aiping Tong;Shuaiyao Lu;Xiaozhong Peng;Xiawei Wei

作者机构：Laboratory of Aging Research and Cancer Drug TargetingState Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengduSichuan610041China National Kunming High-level Biosafety Primate Research CenterInstitute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina Westvac Biopharm Co.Ltd.No.618Fenghuang RoadShuangliu DistrictChengduSichuanChina Division of Animal Model ResearchInstitute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control102629BeijingChina State Key Laboratory of Medical Molecular BiologyDepartment of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2022年第19卷第5期

页      面：577-587页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Science Foundation for Excellent Young Scholars (32122052) National Natural Science Foundation Regional Innovation and Development (No.U19A2003) 

主　　题：COVID-19 SARS-CoV-2 neutrophil extracellular traps histones sialic acid 

摘      要：Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host *** to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse *** histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino *** acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S ***,histones enhance cell-cell ***,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse *** findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.