| Primate-specific fi c BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2 |
| Xu, L ; Yu, DD; Xu, M; Liu, YM; Yang, LX; Zou, QC; Feng, XL; Li, MH; Sheng, NY; Yao, YG
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| 2024
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| 发表期刊 | EBIOMEDICINE
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| ISSN | 2352-3964
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| 卷号 | 107 |
| 摘要 | 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, fl ow 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 fi ed 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 fi ght 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). Copyright (c) 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/14497
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| 专题 | 科研部门_疾病机理遗传学和进化医学学科组（姚永刚）
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推荐引用方式
GB/T 7714 |
Xu, L,Yu, DD,Xu, M,et al. Primate-specific fi c BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2[J]. EBIOMEDICINE,2024,107.
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| APA |
Xu, L.,Yu, DD.,Xu, M.,Liu, YM.,Yang, LX.,...&Yao, YG.(2024).Primate-specific fi c BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2.EBIOMEDICINE,107.
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| MLA |
Xu, L,et al."Primate-specific fi c BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2".EBIOMEDICINE 107(2024).
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