Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
Biomedical Translation Research Center, Academia Sinica, Taipei, 11529, Taiwan.
J Biomed Sci. 2023 Oct 12;30(1):87. doi: 10.1186/s12929-023-00980-w.
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.
We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission.
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.
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.
人类血管紧张素转换酶 2（hACE2）是介导严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的受体。hACE2 在肺部的表达水平较低，在 SARS-CoV-2 感染后上调。这种 hACE2 受限的肺部环境如何支持病毒的有效传播，以及 hACE2 表达的动态变化如何影响 SARS-CoV-2 感染，目前尚不清楚。
我们生成了具有不同 hACE2 表达水平的稳定细胞系，以评估 hACE2 表达水平如何影响 SARS-CoV-2 的传播。
我们证明了 hACE2 表达水平控制着 SARS-CoV-2 传播的方式。hACE2 受限的细胞在 SARS-CoV-2 脱落方面具有优势，从而导致无细胞传播。相比之下，增强的 hACE2 表达促进了 SARS-CoV-2 的细胞间传播。此外，这种细胞间传播可能是由包含 hACE2 的小泡介导的，这些小泡容纳了大量的 SARS-CoV-2 病毒颗粒，并通过细胞间延伸将它们运输到邻近的细胞。
这种 hACE2 介导的无细胞和细胞间传播途径之间的转换，为 SARS-CoV-2 提供了有利于病毒传播或逃避体液免疫的优势，从而导致了 COVID-19 大流行和发病机制。
