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

tetano

Editor, Senior Moderator
J Biomed Sci


. 2023 Oct 12;30(1):87.
doi: 10.1186/s12929-023-00980-w. Human ACE2 protein is a molecular switch controlling the mode of SARS-CoV-2 transmission

Chao-Fu Yang[SUP] 1 [/SUP], Chun-Che Liao[SUP] #[/SUP][SUP] 2 3 [/SUP], Hung-Wei Hsu[SUP] #[/SUP][SUP] 2 [/SUP], Jian-Jong Liang[SUP] #[/SUP][SUP] 2 [/SUP], Chih-Shin Chang[SUP] 2 3 [/SUP], Hui-Ying Ko[SUP] 2 [/SUP], Rue-Hsin Chang[SUP] 2 [/SUP], Wei-Chun Tang[SUP] 4 [/SUP], Ming-Hao Chang[SUP] 2 [/SUP], I-Hsuan Wang[SUP] 5 [/SUP], Yi-Ling Lin[SUP] 6 7 [/SUP]



Affiliations
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.

Keywords: ACE2; COVID-19; Cell-free transmission; Cell-to-cell transmission; SARS-CoV-2.

 
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