L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus.
L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus.
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DOI：
10.1172/jci.insight.148999
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发表时间：
2021-07-22
期刊：
影响因子：
8
通讯作者：
Xia L
中科院分区：
文献类型：
--
作者：
Kondo Y;Larabee JL;Gao L;Shi H;Shao B;Hoover CM;McDaniel JM;Ho YC;Silasi-Mansat R;Archer-Hartmann SA;Azadi P;Srinivasan RS;Rezaie AR;Borczuk A;Laurence JC;Lupu F;Ahamed J;McEver RP;Papin JF;Yu Z;Xia L
由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）仍处于大流行状态。严重的疾病与多器官功能障碍有关，但一些感染细胞不表达ACE2，这是SARS-CoV-2的典型进入受体。在这里，我们报道了c型凝集素受体L-SIGN以Ca2+依赖的方式与高甘露糖型n -聚糖在SARS-CoV-2刺突蛋白上相互作用。我们发现L-SIGN在人肝窦内皮细胞（LSECs）和淋巴结淋巴内皮细胞上高表达，而在血液内皮细胞上不表达。利用高分辨率共聚焦显微镜成像，我们在COVID-19患者肝脏尸检样本的LSECs中检测到SARS-CoV-2病毒蛋白。我们发现，与对照细胞相比，被SARS-CoV-2刺突蛋白包裹的伪型病毒和真正的SARS-CoV-2病毒都感染了表达l - sign的细胞。阻断L-SIGN功能可降低cov -2型感染。这些结果表明L-SIGN是SARS-CoV-2感染的受体。LSECs是凝血因子vWF和凝血因子FVIII的主要来源。来自COVID-19患者肝脏尸检样本的LSECs表达的vWF和FVIII水平明显高于来自未感染肝脏样本的LSECs。我们的数据表明，L-SIGN是SARS-CoV-2的内皮细胞受体，可能导致covid -19相关的凝血功能障碍。
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a pandemic. Severe disease is associated with dysfunction of multiple organs, but some infected cells do not express ACE2, the canonical entry receptor for SARS-CoV-2. Here, we report that the C-type lectin receptor L-SIGN interacted in a Ca2+-dependent manner with high-mannose–type N-glycans on the SARS-CoV-2 spike protein. We found that L-SIGN was highly expressed on human liver sinusoidal endothelial cells (LSECs) and lymph node lymphatic endothelial cells but not on blood endothelial cells. Using high-resolution confocal microscopy imaging, we detected SARS-CoV-2 viral proteins within the LSECs from liver autopsy samples from patients with COVID-19. We found that both pseudo-typed virus enveloped with SARS-CoV-2 spike protein and authentic SARS-CoV-2 virus infected L-SIGN–expressing cells relative to control cells. Moreover, blocking L-SIGN function reduced CoV-2–type infection. These results indicate that L-SIGN is a receptor for SARS-CoV-2 infection. LSECs are major sources of the clotting factors vWF and factor VIII (FVIII). LSECs from liver autopsy samples from patients with COVID-19 expressed substantially higher levels of vWF and FVIII than LSECs from uninfected liver samples. Our data demonstrate that L-SIGN is an endothelial cell receptor for SARS-CoV-2 that may contribute to COVID-19–associated coagulopathy.
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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：
64.5
作者：
Fauver, Joseph R.;Petrone, Mary E.;Grubaugh, Nathan D.
通讯作者：
Grubaugh, Nathan D.
超越屏蔽：聚糖在SARS-COV-2尖峰蛋白中的作用。
影响因子：
18.2
作者：
Casalino L;Gaieb Z;Goldsmith JA;Hjorth CK;Dommer AC;Harbison AM;Fogarty CA;Barros EP;Taylor BC;McLellan JS;Fadda E;Amaro RE
通讯作者：
Amaro RE
影响因子：
30.8
作者：
Chan VS;Chan KY;Chen Y;Poon LL;Cheung AN;Zheng B;Chan KH;Mak W;Ngan HY;Xu X;Screaton G;Tam PK;Austyn JM;Chan LC;Yip SP;Peiris M;Khoo US;Lin CL
通讯作者：
Lin CL
影响因子：
7.3
作者：
Colombat, M;Paradis, V;Bedossa, P
通讯作者：
Bedossa, P