tetano
Editor, Senior Moderator
JCI Insight
. 2021 Jul 22;6(14):148999.
doi: 10.1172/jci.insight.148999.
L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus
Yuji Kondo[SUP] 1 [/SUP], Jason L Larabee[SUP] 2 [/SUP], Liang Gao[SUP] 1 [/SUP], Huiping Shi[SUP] 1 [/SUP], Bojing Shao[SUP] 1 [/SUP], Christopher M Hoover[SUP] 1 3 [/SUP], J Michael McDaniel[SUP] 1 [/SUP], Yen-Chun Ho[SUP] 1 [/SUP], Robert Silasi-Mansat[SUP] 1 [/SUP], Stephanie A Archer-Hartmann[SUP] 4 [/SUP], Parastoo Azadi[SUP] 4 [/SUP], R Sathish Srinivasan[SUP] 1 [/SUP], Alireza R Rezaie[SUP] 1 3 [/SUP], Alain Borczuk[SUP] 5 [/SUP], Jeffrey C Laurence[SUP] 6 [/SUP], Florea Lupu[SUP] 1 7 [/SUP], Jasimuddin Ahamed[SUP] 1 8 [/SUP], Rodger P McEver[SUP] 1 3 [/SUP], James F Papin[SUP] 7 [/SUP], Zhongxin Yu[SUP] 7 [/SUP], Lijun Xia[SUP] 1 3 [/SUP]
Affiliations
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: Cell Biology; Coagulation; Endothelial cells; Vascular Biology.
. 2021 Jul 22;6(14):148999.
doi: 10.1172/jci.insight.148999.
L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus
Yuji Kondo[SUP] 1 [/SUP], Jason L Larabee[SUP] 2 [/SUP], Liang Gao[SUP] 1 [/SUP], Huiping Shi[SUP] 1 [/SUP], Bojing Shao[SUP] 1 [/SUP], Christopher M Hoover[SUP] 1 3 [/SUP], J Michael McDaniel[SUP] 1 [/SUP], Yen-Chun Ho[SUP] 1 [/SUP], Robert Silasi-Mansat[SUP] 1 [/SUP], Stephanie A Archer-Hartmann[SUP] 4 [/SUP], Parastoo Azadi[SUP] 4 [/SUP], R Sathish Srinivasan[SUP] 1 [/SUP], Alireza R Rezaie[SUP] 1 3 [/SUP], Alain Borczuk[SUP] 5 [/SUP], Jeffrey C Laurence[SUP] 6 [/SUP], Florea Lupu[SUP] 1 7 [/SUP], Jasimuddin Ahamed[SUP] 1 8 [/SUP], Rodger P McEver[SUP] 1 3 [/SUP], James F Papin[SUP] 7 [/SUP], Zhongxin Yu[SUP] 7 [/SUP], Lijun Xia[SUP] 1 3 [/SUP]
Affiliations
- PMID: 34291736
- DOI: 10.1172/jci.insight.148999
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: Cell Biology; Coagulation; Endothelial cells; Vascular Biology.