Human ACE2 protein is a molecular switch controlling the mode of SARS-CoV-2 transmission

Autor: Chao-Fu Yang, Chun-Che Liao, Hung-Wei Hsu, Jian-Jong Liang, Chih-Shin Chang, Hui-Ying Ko, Rue-Hsin Chang, Wei-Chun Tang, Ming-Hao Chang, I-Hsuan Wang, Yi-Ling Lin
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Biomedical Science, Vol 30, Iss 1, Pp 1-13 (2023)
Druh dokumentu: article
ISSN: 1423-0127
DOI: 10.1186/s12929-023-00980-w
Popis: Abstract Background Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the lungs and is upregulated after SARS-CoV-2 infection. How such a hACE2-limited pulmonary environment supports efficient virus transmission and how dynamic hACE2 expression affects SARS-CoV-2 infection are unclear. Methods We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission. Results We demonstrated that the hACE2 expression level controls the mode of SARS-CoV-2 transmission. The hACE2-limited cells have an advantage for SARS-CoV-2 shedding, which leads to cell-free transmission. By contrast, enhanced hACE2 expression facilitates the SARS-CoV-2 cell-to-cell transmission. Furthermore, this cell-to-cell transmission is likely facilitated by hACE2-containing vesicles, which accommodate numerous SARS-CoV-2 virions and transport them to neighboring cells through intercellular extensions. Conclusions This hACE2-mediated switch between cell-free and cell-to-cell transmission routes provides SARS-CoV-2 with advantages for either viral spread or evasion of humoral immunity, thereby contributing to the COVID-19 pandemic and pathogenesis.
Databáze: Directory of Open Access Journals
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