tetano
Editor, Senior Moderator
EBioMedicine
. 2024 Aug 13:107:105281.
doi: 10.1016/j.ebiom.2024.105281. Online ahead of print. Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2
Ling Xu[SUP] 1 [/SUP], Dandan Yu[SUP] 2 [/SUP], Min Xu[SUP] 3 [/SUP], Yamin Liu[SUP] 3 [/SUP], Lu-Xiu Yang[SUP] 4 [/SUP], Qing-Cui Zou[SUP] 5 [/SUP], Xiao-Li Feng[SUP] 5 [/SUP], Ming-Hua Li[SUP] 5 [/SUP], Nengyin Sheng[SUP] 6 [/SUP], Yong-Gang Yao[SUP] 7 [/SUP]
Affiliations
Background: 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.
Methods: 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.
Findings: 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.
Interpretation: 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.
Funding: 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).
Keywords: ACE2; BTN3A2; COVID-19; SARS-CoV-2; Spike protein.
. 2024 Aug 13:107:105281.
doi: 10.1016/j.ebiom.2024.105281. Online ahead of print. Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2
Ling Xu[SUP] 1 [/SUP], Dandan Yu[SUP] 2 [/SUP], Min Xu[SUP] 3 [/SUP], Yamin Liu[SUP] 3 [/SUP], Lu-Xiu Yang[SUP] 4 [/SUP], Qing-Cui Zou[SUP] 5 [/SUP], Xiao-Li Feng[SUP] 5 [/SUP], Ming-Hua Li[SUP] 5 [/SUP], Nengyin Sheng[SUP] 6 [/SUP], Yong-Gang Yao[SUP] 7 [/SUP]
Affiliations
- PMID: 39142074
- DOI: 10.1016/j.ebiom.2024.105281
Background: 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.
Methods: 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.
Findings: 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.
Interpretation: 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.
Funding: 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).
Keywords: ACE2; BTN3A2; COVID-19; SARS-CoV-2; Spike protein.