CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells.
CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells.
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DOI：
10.1038/s41392-020-00426-x
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发表时间：
2020-12-04
影响因子：
39.3
通讯作者：
Chen ZN
中科院分区：
文献类型：
--
作者：
Wang K;Chen W;Zhang Z;Deng Y;Lian JQ;Du P;Wei D;Zhang Y;Sun XX;Gong L;Yang X;He L;Zhang L;Yang Z;Geng JJ;Chen R;Zhang H;Wang B;Zhu YM;Nan G;Jiang JL;Li L;Wu J;Lin P;Huang W;Xie L;Zheng ZH;Zhang K;Miao JL;Cui HY;Huang M;Zhang J;Fu L;Yang XM;Zhao Z;Sun S;Gu H;Wang Z;Wang CF;Lu Y;Liu YY;Wang QY;Bian H;Zhu P;Chen ZN
面对与COVID-19的持久战和SARS-CoV-2的快速演变，迄今为止尚未有治疗该疾病的特效药物报道。血管紧张素转换酶 2 (ACE2) 是 SARS-CoV-2 的受体，通过与刺突蛋白结合介导病毒感染。尽管ACE2在肺、肾和肠中表达，但其表达水平相当低，尤其是在肺中。考虑到COVID-19的巨大传染性，我们推测SARS-CoV-2可能依赖其他途径来促进其感染。在这里，我们首先发现宿主细胞受体 CD147 和 SARS-CoV-2 刺突蛋白之间的相互作用。抗 CD147 抗体 Meplazumab 在 Vero E6 和 BEAS-2B 细胞系中丢失 CD147 或阻断 CD147，可抑制 SARS-CoV-2 扩增。人 CD147 的表达允许病毒进入不敏感的 BHK-21 细胞，该细胞可以被 CD147 胞外片段中和。在感染 SARS-CoV-2 的人 CD147 (hCD147) 小鼠的肺部可检测到病毒载量，但在感染病毒的野生型小鼠的肺部却检测不到病毒载量。有趣的是，在 COVID-19 患者肺组织的淋巴细胞中观察到病毒粒子。具有 ACE2 天然缺陷特性的人类 T 细胞可以以剂量依赖性方式感染 SARS-CoV-2 假病毒，而 Meplazumab 可特异性抑制这种感染。此外，CD147介导病毒通过内吞作用进入宿主细胞。总之，我们的研究揭示了一种新的病毒进入途径，即 CD147 刺突蛋白，它为开发针对 COVID-19 的特异性有效药物提供了重要靶点。
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
6.1
作者：
Liu, Kui;Fang, Yuan-Yuan;Liu, Hui-Guo
通讯作者：
Liu, Hui-Guo
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
--
作者：
Hulswit RJ;de Haan CA;Bosch BJ
通讯作者：
Bosch BJ
影响因子：
2.3
作者：
Barth, K.;Blaesche, R.;Kasper, M.
通讯作者：
Kasper, M.