L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus

Autor: Yuji Kondo, Jason L. Larabee, Liang Gao, Huiping Shi, Bojing Shao, Christopher M. Hoover, J. Michael McDaniel, Yen-Chun Ho, Robert Silasi-Mansat, Stephanie A. Archer-Hartmann, Parastoo Azadi, R. Sathish Srinivasan, Alireza R. Rezaie, Alain Borczuk, Jeffrey C. Laurence, Florea Lupu, Jasimuddin Ahamed, Rodger P. McEver, James F. Papin, Zhongxin Yu, Lijun Xia
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: JCI Insight, Vol 6, Iss 14 (2021)
Druh dokumentu: article
ISSN: 2379-3708
DOI: 10.1172/jci.insight.148999
Popis: 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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