- 作者: 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
- 作者服務機構: 1.Biomedical Translation Research Center, Academia Sinica, Taipei, 11529, Taiwan 2.Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan 3.Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: SARS-CoV-2, COVID-19, ACE2, Cell-free transmission, Cell-to-cell transmission