A Transmembrane Serine Protease Is Linked to the Severe Acute Respiratory Syndrome Coronavirus Receptor and Activates Virus Entry
A Transmembrane Serine Protease Is Linked to the Severe Acute Respiratory Syndrome Coronavirus Receptor and Activates Virus Entry
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DOI：
10.1128/jvi.02062-10
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Gallagher, Tom
中科院分区：
文献类型：
--
作者：
Shulla, Ana;Heald-Sargent, Taylor;Gallagher, Tom
刺突(S)蛋白是包膜冠状病毒（cov）的决定性突起，通过将病毒连接到质膜受体并催化随后的病毒-细胞膜融合来介导细胞进入。后一种膜融合需要S蛋白构象的灵活性，这是由蛋白水解裂解促进的。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。人类严重急性呼吸综合征冠状病毒（SARS）冠状病毒的主要受体是血管紧张素转换酶2 （ACE2）。ACE2免疫沉淀捕获跨膜蛋白酶/丝氨酸亚家族成员2 (TMPRSS2)，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促进SARS s型假HIV和真实SARS- cov的细胞进入。增强的入口与tmprss2介导的S和ACE2蛋白水解有关。这些发现表明，由初级受体和单独的内源性蛋白酶组成的细胞表面复合体作为激活sars冠状病毒进入细胞的门户。
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.