{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["107"],"submitter":["Xu L"],"pubmed_abstract":["<h4>Background</h4>Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics.<h4>Methods</h4>We analyzed human lung single-cell RNA sequencing dataset to discern the association of butyrophilin subfamily 3 member A2 (BTN3A2) expression with COVID-19. The BTN3A2 gene edited cell lines and transgenic mice were infected by live SARS-CoV-2 in a biosafety level 3 (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry and competition ELISA assays were performed in BTN3A2 gene edited cells. We performed quantitative real-time PCR, histological and/or immunohistochemical analyses for tissue samples from mice with or without SARS-CoV-2 infection.<h4>Findings</h4>The BTN3A2 mRNA level was correlated with COVID-19 severity. BTN3A2 expression was predominantly identified in epithelial cells, elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same lung cell subtypes. BTN3A2 targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in vivo.<h4>Interpretation</h4>These results reveal a key role of BTN3A2 in the fight against COVID-19. Identifying potential monoclonal antibodies which mimic BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19.<h4>Funding</h4>This study was supported by the National Natural Science Foundation of China (32070569, U1902215, and 32371017), the CAS \"Light of West China\" Program, and Yunnan Province (202305AH340006)."],"journal":["EBioMedicine"],"pagination":["105281"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11367481"],"repository":["biostudies-literature"],"pubmed_title":["Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2."],"pmcid":["PMC11367481"],"pubmed_authors":["Xu L","Liu Y","Li MH","Xu M","Zou QC","Yang LX","Feng XL","Sheng N","Yu D","Yao YG"],"additional_accession":[]},"is_claimable":false,"name":"Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2.","description":"<h4>Background</h4>Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics.<h4>Methods</h4>We analyzed human lung single-cell RNA sequencing dataset to discern the association of butyrophilin subfamily 3 member A2 (BTN3A2) expression with COVID-19. The BTN3A2 gene edited cell lines and transgenic mice were infected by live SARS-CoV-2 in a biosafety level 3 (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry and competition ELISA assays were performed in BTN3A2 gene edited cells. We performed quantitative real-time PCR, histological and/or immunohistochemical analyses for tissue samples from mice with or without SARS-CoV-2 infection.<h4>Findings</h4>The BTN3A2 mRNA level was correlated with COVID-19 severity. BTN3A2 expression was predominantly identified in epithelial cells, elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same lung cell subtypes. BTN3A2 targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in vivo.<h4>Interpretation</h4>These results reveal a key role of BTN3A2 in the fight against COVID-19. Identifying potential monoclonal antibodies which mimic BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19.<h4>Funding</h4>This study was supported by the National Natural Science Foundation of China (32070569, U1902215, and 32371017), the CAS \"Light of West China\" Program, and Yunnan Province (202305AH340006).","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-07-02T03:14:46.054Z","creation":"2025-04-05T12:31:25.653Z"},"accession":"S-EPMC11367481","cross_references":{"pubmed":["39142074"],"doi":["10.1016/j.ebiom.2024.105281"]}}