SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.
SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.
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DOI：
10.1074/jbc.m508381200
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发表时间：
2006-02-10
期刊：
影响因子：
--
通讯作者：
Choe H
中科院分区：
文献类型：
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作者：
Huang IC;Bosch BJ;Li F;Li W;Lee KH;Ghiran S;Vasilieva N;Dermody TS;Harrison SC;Dormitzer PR;Farzan M;Rottier PJ;Choe H
病毒需要特定的细胞受体来感染它们的靶细胞。血管紧张素转换酶2（ACE 2）是SARS冠状病毒（SARS-CoV）和人冠状病毒NL 63（HCoV-NL 63）两种不同冠状病毒的细胞受体。除了宿主细胞受体外，溶酶体半胱氨酸蛋白酶也是某些病毒产生性感染所必需的。在这里，我们表明，SARS冠状病毒，而不是HCoV-NL 63，利用半胱氨酸蛋白酶组织蛋白酶L的酶活性感染ACE 2表达细胞。组织蛋白酶L抑制剂阻断了SARS-CoV和用SARS-CoV刺突蛋白假型化的逆转录病毒的感染，但不能阻断HCoV-NL 63或用HCoV-NL 63 S蛋白假型化的逆转录病毒的感染。外源性组织蛋白酶L的表达显著增强了由SARS-CoV S蛋白和丝状病毒GP蛋白介导的感染，但不增强由HCoV-NL 63 S蛋白或水疱性口炎病毒G蛋白介导的感染。最后，内体酸化的抑制剂对HCoV-NL 63 S蛋白介导的感染的影响远小于对SARS-CoV S蛋白介导的感染的影响。我们的数据表明，两种利用共同受体的冠状病毒通过不同的机制进入细胞。
Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.