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

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...

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Published in:JCI insight Vol. 6; no. 14
Main Authors: Kondo, Yuji, Larabee, Jason L., Gao, Liang, Shi, Huiping, Shao, Bojing, Hoover, Christopher M., McDaniel, J. Michael, Ho, Yen-Chun, Silasi-Mansat, Robert, Archer-Hartmann, Stephanie A., Azadi, Parastoo, Srinivasan, R. Sathish, Rezaie, Alireza R., Borczuk, Alain, Laurence, Jeffrey C., Lupu, Florea, Ahamed, Jasimuddin, McEver, Rodger P., Papin, James F., Yu, Zhongxin, Xia, Lijun
Format: Journal Article
Language:English
Published: Ann Arbor American Society for Clinical Investigation 22.07.2021
American Society for Clinical investigation
Subjects:
ACE2
Amino acids
Angiotensin-converting enzyme 2
Autopsies
Autopsy
Calcium
Calcium channels (C-type)
Cell biology
Clotting
Coagulation factors
Confocal microscopy
Coronaviruses
COVID-19
Endothelial cells
Flow cytometry
Glycosylation
Hepatocytes
Infections
Lectins
Liver
Lymph nodes
Lymphatic system
Mannose
N-glycans
Pandemics
Polysaccharides
Proteins
Severe acute respiratory syndrome coronavirus 2
Spike protein
Thrombosis
Vascular biology
Viruses
ISSN:2379-3708, 2379-3708
Online Access:Get full text
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Summary: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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ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.148999