State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Nat Commun. 2021 Jan 8;12(1):134. doi: 10.1038/s41467-020-20457-w.
Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.
了解导致 SARS-CoV-2 有效感染人体细胞的因素，可能有助于我们深入了解 SARS-CoV-2 的传染性和发病机制，并揭示干预靶点。在这里，我们分析了宿主和病毒决定因素，这些因素对于 SARS-CoV-2 在人肺上皮细胞和离体人肺组织中的有效感染是必不可少的。我们确定肝素硫酸盐是 SARS-CoV-2 感染的重要附着因子。接下来，我们表明，存在于 ACE2 上的唾液酸会阻碍刺突/ACE2 相互作用的效率。虽然 SARS-CoV 在人肺上皮细胞和离体人肺组织中的感染受到唾液酸介导的限制，但 SARS-CoV-2 的感染受到的限制程度较小。我们进一步证明，SARS-CoV-2 刺突中的类弗林蛋白酶切割位点对于病毒在人肺组织中的有效复制是必需的，但不是在肠道组织中。这些发现为 SARS-CoV-2 有效感染人肺提供了见解。
