HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry

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.Wei et al. identify the HDL receptor SR-B1 as a host factor that enhances infection of cultured cells with SARS-CoV-2 in the presence of ACE2, thus providing a possible molecular connection between lipoprotein metabolism and COVID-19.

严重急性呼吸综合征冠状病毒2（SARS - CoV - 2）是导致正在发生的2019冠状病毒病（COVID - 19）大流行的病原体，它通过病毒刺突蛋白（SARS - 2 - S）与细胞表面受体血管紧张素转换酶2（ACE2）结合来感染宿主细胞。在此我们表明，高密度脂蛋白（HDL）清道夫受体B类1型（SR - B1）促进了SARS - CoV - 2依赖ACE2的进入。我们发现SARS - 2 - S的S1亚基与胆固醇以及可能与HDL成分结合，以增强病毒在体外的摄取。SR - B1的表达通过增强病毒附着促进SARS - CoV - 2进入表达ACE2的细胞。用单克隆抗体阻断SARS - 2 - S1上的胆固醇结合位点，或者用药物性SR - B1拮抗剂处理培养的细胞，可抑制HDL增强的SARS - CoV - 2感染。我们进一步表明，SR - B1与ACE2在人肺组织以及几种肺外组织中共表达。我们的研究结果揭示，SR - B1作为一种宿主因子促进SARS - CoV - 2进入，可能有助于解释病毒嗜性，确定COVID - 19与脂蛋白代谢之间可能存在的分子联系，并强调SR - B1是干扰SARS - CoV - 2感染的一个潜在治疗靶点。魏等人确定HDL受体SR - B1是一种宿主因子，在ACE2存在的情况下增强SARS - CoV - 2对培养细胞的感染，从而提供了脂蛋白代谢与COVID - 19之间可能存在的分子联系。