ArticleCellular & molecular immunology2022
Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells.
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Article in Cellular & molecular immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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29citing papers in PubMed, 1 pooled it
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Programmed cell death in human respiratory syncytial virus infection.Frontiers in cellular and infection microbiology · 2025Pooled it
- Metatranscriptomics uncovers host immune and microbiome signatures specific to and shared between human metapneumovirus and respiratory syncytial virus infections in children.Virologica Sinica · 2026Article
- Review
- Article
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Neutrophil Extracellular Traps (NETs) in health and disease.Molecular biomedicine · 2025Review
- The role of neutrophils in vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: Is it time for a SAH clinical trial targeting neutrophils?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Review
- Magnitude of SARS-CoV-2 Antibody Production and Its Relationship with Autoantibody Formation.Infectious diseases & clinical microbiology · 2025Article
- Review
- Sars-Cov-2 spike protein and plasma from COVID-19 patients induce extracellular traps by myeloid-derived suppressor cells.Frontiers in cellular and infection microbiology · 2025Article
- Advances in adhesion-related pathogenesis inFrontiers in microbiology · 2025Review
- Dynamic Gene Attention Focus (DyGAF): Enhancing Biomarker Identification Through Dual-Model Attention Networks.Bioinformatics and biology insights · 2025Article
- SARS-CoV-2 Delta and Omicron variants resist spike cleavage by human airway trypsin-like protease.The Journal of clinical investigation · 2024Article
- Neutrophil Extracellular Traps and Respiratory Disease.Journal of clinical medicine · 2024Review
- Composition and Function of Neutrophil Extracellular Traps.Biomolecules · 2024Review
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- Predictive Value of dsDNA and Nucleosomes as Neutrophil Extracellular Traps-Related Biomarkers for COVID-19 in Older Patients.Journal of inflammation research · 2024Article
- The role of cell death in SARS-CoV-2 infection.Signal transduction and targeted therapy · 2023Review
- Review
- Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants.Nature communications · 2023Article
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Authors and funding
57 authors at 4 institutions in 1 country.
Weiqi Hong *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.ORCID http://orcid.org/0000-0003-1668-2301
Jingyun Yang *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.
Jun Zou *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.
Zhenfei Bi *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.
Cai He *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.
Hong Lei *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.
Xuemei HeLaboratory 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.
Xue LiLaboratory 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.
Aqu AluLaboratory 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.
Wenyan RenLaboratory 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.
Zeng WangLaboratory 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.
Xiaohua JiangLaboratory 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.
Kunhong ZhongLaboratory 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.
Guowen JiaLaboratory 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.
Yun YangNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Wenhai YuNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Qing HuangNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Mengli YangNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Yanan ZhouNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Yuan ZhaoNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Dexuan KuangNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Junbin WangNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Haixuan WangNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Siyuan ChenLaboratory 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.
Min LuoLaboratory 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.ORCID http://orcid.org/0000-0002-6875-7945
Ziqi ZhangLaboratory 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.
Tianqi LuLaboratory 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 ChenLaboratory 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.
Haiying QueLaboratory 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.
Zhiyao HeLaboratory 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.
Qiu SunLaboratory 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.
Wei WangLaboratory 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.
Guobo ShenLaboratory 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.
Guangwen LuLaboratory 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.
Zhiwei ZhaoLaboratory 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 YangLaboratory 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.
Jinliang YangLaboratory 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.
Zhenling WangLaboratory 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.
Jiong LiLaboratory 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.
Xiangrong SongLaboratory 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.
Lunzhi DaiLaboratory 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.ORCID http://orcid.org/0000-0002-3003-8910
Chong ChenLaboratory 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 GengLaboratory 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.
Maling GouLaboratory 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 ChenLaboratory 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.
Haohao DongLaboratory 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.ORCID http://orcid.org/0000-0002-5022-3494
Yong PengLaboratory 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.
Canhua HuangLaboratory 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.ORCID http://orcid.org/0000-0003-2247-7750
Zhiyong QianLaboratory 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.
Wei ChengLaboratory 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.
Changfa FanDivision of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, 102629, Beijing, China.
Yuquan WeiLaboratory 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.
Zhaoming SuLaboratory 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.
Aiping TongLaboratory 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. aipingtong@scu.edu.cn.
Shuaiyao LuNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China. lushuaiyao-km@163.com.ORCID http://orcid.org/0000-0003-1675-9735
Xiaozhong PengNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China. pengxiaozhong@pumc.edu.cn.
Xiawei WeiLaboratory 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. xiaweiwei@scu.edu.cn.ORCID http://orcid.org/0000-0002-6513-6422
Sichuan University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNHuawei Technologies (China) · CNNational Institutes for Food and Drug Control · CN
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
COVID-19SARS-CoV-2AnimalsHistonesMiceN-Acetylneuraminic AcidProtein SubunitsSpike Glycoprotein, CoronavirusVirus InternalizationHistonesN-Acetylneuraminic AcidProtein SubunitsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2COVID-19histonesneutrophil extracellular trapsSARS-CoV-2sialic acid
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