{"doi":"10.1128/jvi.02015-19","title":"Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry","abstract":"<jats:p>Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.</jats:p>","journal":"Journal of Virology","year":2020,"id":17301,"datarank":13.161744934534294,"base_score":6.556778356158042,"endowment":6.556778356158042,"self_citation_contribution":0.9835167534237065,"citation_network_contribution":12.178228181110587,"self_endowment_contribution":0.9835167534237065,"citer_contribution":12.178228181110587,"corpus_percentile":null,"corpus_rank":null,"citation_count":703,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":4,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":96771,"name":"Jian Shang","orcid":null,"position":1,"is_corresponding":false},{"id":124273,"name":"Shihui Sun","orcid":null,"position":2,"is_corresponding":false},{"id":105102,"name":"Wanbo Tai","orcid":null,"position":3,"is_corresponding":false},{"id":17699,"name":"Jing Chen","orcid":"0000-0001-5972-3623","position":4,"is_corresponding":false},{"id":103760,"name":"Qibin Geng","orcid":"0000-0003-4872-2400","position":5,"is_corresponding":false},{"id":105103,"name":"Lei He","orcid":"0000-0001-6955-0121","position":6,"is_corresponding":false},{"id":89760,"name":"Yuehong Chen","orcid":"0000-0003-1948-6867","position":7,"is_corresponding":false},{"id":77881,"name":"Jianming Wu","orcid":"0000-0001-9142-7066","position":8,"is_corresponding":false},{"id":17722,"name":"Zheng‐Li Shi","orcid":"0000-0001-8089-163X","position":9,"is_corresponding":false},{"id":105108,"name":"Yusen Zhou","orcid":"0000-0002-7301-4089","position":10,"is_corresponding":false},{"id":105109,"name":"Lanying Du","orcid":"0000-0001-5955-1294","position":11,"is_corresponding":false},{"id":103706,"name":"Fang Li","orcid":"0000-0002-1958-366X","position":12,"is_corresponding":false},{"id":103703,"name":"Yushun Wan","orcid":"0000-0003-0496-6315","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":6.556778356158042,"endowment":6.556778356158042,"datacite_reuse_total":4,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31826992","pmcid":"PMC7022351","openalex_id":"https://openalex.org/W2995449088","authors":[],"funders":[{"funder_name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","grant_id":"R01AI089728","title":null},{"funder_name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","grant_id":"R01AI110700","title":null},{"funder_name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","grant_id":"R01AI139092","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01AI139092-04","title":"Structure-based design of coronavirus subunit vaccines"},{"funder_name":"National Institutes of Health","grant_id":"5R01AI089728-07","title":"Receptor recognition and cell entry of coronaviruses"},{"funder_name":"National Institutes of Health","grant_id":"1R01AI110700-01A1","title":"Mechanisms of MERS-CoV Entry, Cross-species Transmission and Pathogenesis"}],"total_grants":6,"fwci":85.4811,"citation_percentile":0.99969189,"influential_citations":39,"citation_trend":[{"year":2018,"count":1},{"year":2020,"count":341},{"year":2021,"count":164},{"year":2022,"count":86},{"year":2023,"count":49},{"year":2024,"count":33},{"year":2025,"count":19},{"year":2026,"count":10}],"oa_status":"green","license":"ASM Journals Non-Commercial TDM","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7022351","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc7022351?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7022351","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02015-19","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.02015-19","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31826992","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7022351","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7022351?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1128/jvi.02015-19","host_type":""},{"url":"http://dx.doi.org/10.1128/JVI.02015-19","host_type":""},{"url":"https://dx.doi.org/10.1128/jvi.02015-19","host_type":""}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","Animal Virus Infections Studies","Viral gastroenteritis research and epidemiology","Biology","Medicine","0301 basic medicine","03 medical and health sciences","Antibodies, Monoclonal","Antibodies, Neutralizing","Antibodies, Viral","Antibody-Dependent Enhancement","Cell Line","Dipeptidyl Peptidase 4","Humans","Immunoglobulin Fab Fragments","Middle East Respiratory Syndrome Coronavirus","Peptide Hydrolases","Proprotein Convertases","Protein Conformation","Protein Domains","Protein Multimerization","Receptors, Fc","Receptors, IgG","Receptors, Virus","Spike Glycoprotein, Coronavirus","Trypsin","Virus Internalization"],"mesh_terms":["Protein Domains","Antibodies, Monoclonal","Antibodies, Viral","Cell Line","Humans","Immunoglobulin Fab Fragments","Peptide Hydrolases","Protein Conformation","Receptors, Fc","Receptors, Virus","Trypsin","Receptors, IgG","Dipeptidyl Peptidase 4","Antibody-Dependent Enhancement","Proprotein Convertases","Virus Internalization","Protein Multimerization","Antibodies, Neutralizing","Spike Glycoprotein, Coronavirus","Middle East Respiratory Syndrome Coronavirus"],"keywords":["Biology","Coronavirus","Mechanism (biology)","Coronavirus disease 2019 (COVID-19)","Virology","Antibody","Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)","2019-20 coronavirus outbreak","Betacoronavirus","Severe acute respiratory syndrome coronavirus","Coronavirus Infections","Genetics","Outbreak","Spike protein","Neutralizing antibody","SARS coronavirus","Viral receptor","Mers Coronavirus","Igg Fc Receptor","Antibody-dependent Enhancement Of Viral Entry","Protein Conformation","Dipeptidyl Peptidase 4","Immunology","Receptors, Fc","Antibodies, Viral","Microbiology","Cell Line","Immunoglobulin Fab Fragments","Protein Domains","Humans","Trypsin","Receptors, IgG","Antibodies, Monoclonal","Virus Internalization","Antibodies, Neutralizing","Antibody-Dependent Enhancement","Virus-Cell Interactions","Insect Science","Spike Glycoprotein, Coronavirus","Middle East Respiratory Syndrome Coronavirus","Receptors, Virus","Proprotein Convertases","Protein Multimerization","Peptide Hydrolases"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.19112860.v1","title":"Additional file 1 of Clinical and antibody characteristics reveal diverse signatures of severe and non-severe SARS-CoV-2 patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19112860","title":"Additional file 1 of Clinical and antibody characteristics reveal diverse signatures of severe and non-severe SARS-CoV-2 patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19112863.v1","title":"Additional file 2 of Clinical and antibody characteristics reveal diverse signatures of severe and non-severe SARS-CoV-2 patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19112863","title":"Additional file 2 of Clinical and antibody characteristics reveal diverse signatures of severe and non-severe SARS-CoV-2 patients","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"refseq"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-02T18:17:38.545032Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}