L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus.
JCI Insight
; 6(14)2021 07 22.
Article
in English
| MEDLINE | ID: covidwho-1320462
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Capillaries
/
Cell Adhesion Molecules
/
Receptors, Cell Surface
/
Lectins, C-Type
/
Endothelial Cells
/
Lymphatic Vessels
/
SARS-CoV-2
/
COVID-19
/
Liver
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Jci.insight.148999
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