Department of Microbiology and Immunology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
J Virol. 2011 Jan;85(2):873-82. doi: 10.1128/JVI.02062-10. Epub 2010 Nov 10.
Spike (S) proteins, the defining projections of the enveloped coronaviruses (CoVs), mediate cell entry by connecting viruses to plasma membrane receptors and by catalyzing subsequent virus-cell membrane fusions. The latter membrane fusion requires an S protein conformational flexibility that is facilitated by proteolytic cleavages. We hypothesized that the most relevant cellular proteases in this process are those closely linked to host cell receptors. The primary receptor for the human severe acute respiratory syndrome CoV (SARS) CoV is angiotensin-converting enzyme 2 (ACE2). ACE2 immunoprecipitation captured transmembrane protease/serine subfamily member 2 (TMPRSS2), a known human airway and alveolar protease. ACE2 and TMPRSS2 colocalized on cell surfaces and enhanced the cell entry of both SARS S-pseudotyped HIV and authentic SARS-CoV. Enhanced entry correlated with TMPRSS2-mediated proteolysis of both S and ACE2. These findings indicate that a cell surface complex comprising a primary receptor and a separate endoprotease operates as a portal for activation of SARS-CoV cell entry.
刺突（S）蛋白是包膜冠状病毒（CoV）的特有突起，通过将病毒连接到质膜受体并催化随后的病毒-质膜融合来介导细胞进入。后者的膜融合需要 S 蛋白构象的灵活性，这是由蛋白水解切割促进的。我们假设在这个过程中最相关的细胞蛋白酶是那些与宿主细胞受体密切相关的蛋白酶。人类严重急性呼吸系统综合征冠状病毒（SARS-CoV）的主要受体是血管紧张素转换酶 2（ACE2）。ACE2 的免疫沉淀捕获了跨膜蛋白酶/丝氨酸亚家族成员 2（TMPRSS2），这是一种已知的人类气道和肺泡蛋白酶。ACE2 和 TMPRSS2 在细胞表面共定位，并增强了 SARS S 假型 HIV 和真正的 SARS-CoV 的细胞进入。增强的进入与 TMPRSS2 介导的 S 和 ACE2 的蛋白水解相关。这些发现表明，包含主要受体和单独的内肽酶的细胞表面复合物作为 SARS-CoV 细胞进入的激活门户起作用。
