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Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells.
Hong, Weiqi; Yang, Jingyun; Zou, Jun; Bi, Zhenfei; He, Cai; Lei, Hong; He, Xuemei; Li, Xue; Alu, Aqu; Ren, Wenyan; Wang, Zeng; Jiang, Xiaohua; Zhong, Kunhong; Jia, Guowen; Yang, Yun; Yu, Wenhai; Huang, Qing; Yang, Mengli; Zhou, Yanan; Zhao, Yuan; Kuang, Dexuan; Wang, Junbin; Wang, Haixuan; Chen, Siyuan; Luo, Min; Zhang, Ziqi; Lu, Tianqi; Chen, Li; Que, Haiying; He, Zhiyao; Sun, Qiu; Wang, Wei; Shen, Guobo; Lu, Guangwen; Zhao, Zhiwei; Yang, Li; Yang, Jinliang; Wang, Zhenling; Li, Jiong; Song, Xiangrong; Dai, Lunzhi; Chen, Chong; Geng, Jia; Gou, Maling; Chen, Lu; Dong, Haohao; Peng, Yong; Huang, Canhua; Qian, Zhiyong; Cheng, Wei.
  • Hong W; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Yang J; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Zou J; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Bi Z; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • He C; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Lei H; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • He X; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Li X; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Alu A; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Ren W; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Wang Z; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Jiang X; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Zhong K; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Jia G; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Yang Y; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yu W; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Huang Q; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yang M; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Zhou Y; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Zhao Y; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Kuang D; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Wang J; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Wang H; National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Chen S; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Luo M; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Zhang Z; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Lu T; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Chen L; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Que H; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • He Z; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Sun Q; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Wang W; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Shen G; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Lu G; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Zhao Z; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Yang L; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Yang J; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Wang Z; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Li J; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Song X; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Dai L; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Chen C; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Geng J; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Gou M; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Chen L; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Dong H; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Peng Y; Westvac Biopharm Co., Ltd. No. 618, Fenghuang Road, Shuangliu District, Chengdu, Sichuan, China.
  • Huang C; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Qian Z; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
  • Cheng W; Laboratory of Aging Research and Cancer Drug Targeting, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, China.
Cell Mol Immunol ; 19(5): 577-587, 2022 05.
Article in English | MEDLINE | ID: covidwho-1830043
ABSTRACT
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 defense. Contrary 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 model. The 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 acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, 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 model. These 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: Cell Mol Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41423-022-00845-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Animals Language: English Journal: Cell Mol Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41423-022-00845-6