Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, China.
Institute of Physical Science and Information Technology, Anhui University, Hefei, China.
Nat Metab. 2020 Dec;2(12):1391-1400. doi: 10.1038/s42255-020-00324-0. Epub 2020 Nov 26.
Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.
负责当前的 2019 年冠状病毒病（COVID-19）大流行的，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）通过病毒刺突蛋白（SARS-2-S）与细胞表面受体血管紧张素转换酶 2（ACE2）的结合感染宿主细胞。在这里，我们表明高密度脂蛋白（HDL）的清道夫受体 B 型 1（SR-B1）促进了 ACE2 依赖性的 SARS-CoV-2 进入。我们发现 SARS-2-S 的 S1 亚基与胆固醇结合，并可能与 HDL 成分结合，以增强体外病毒摄取。SR-B1 表达通过增强病毒附着促进 SARS-CoV-2 进入 ACE2 表达细胞。用单克隆抗体阻断 SARS-2-S1 上的胆固醇结合位点，或用药理学 SR-B1 拮抗剂处理培养细胞，可抑制 HDL 增强的 SARS-CoV-2 感染。我们进一步表明，SR-B1 与人肺组织和几种肺外组织中的 ACE2 共表达。我们的发现表明，SR-B1 作为一种宿主因子，促进了 SARS-CoV-2 的进入，这可能有助于解释病毒的嗜性，确定 COVID-19 与脂蛋白代谢之间可能存在的分子联系，并突出了 SR-B1 作为干扰 SARS-CoV-2 感染的潜在治疗靶标。
