tetano
Editor, Senior Moderator
EMBO J
. 2021 Sep 12;e106765.
doi: 10.15252/embj.2020106765. Online ahead of print.
Infection and transmission of SARS-CoV-2 depends on heparan sulfate proteoglycans
Marta Bermejo-Jambrina[SUP] 1 [/SUP], Julia Eder[SUP] 1 [/SUP], Tanja M Kaptein[SUP] 1 [/SUP], John L van Hamme[SUP] 1 [/SUP], Leanne C Helgers[SUP] 1 [/SUP], Killian E Vlaming[SUP] 1 [/SUP], Philip J M Brouwer[SUP] 2 [/SUP], Ad C van Nuenen[SUP] 1 [/SUP], Marcel Spaargaren[SUP] 3 [/SUP], Godelieve J de Bree[SUP] 4 [/SUP], Bernadien M Nijmeijer[SUP] 1 [/SUP], Neeltje A Kootstra[SUP] 1 [/SUP], Marit J van Gils[SUP] 2 [/SUP], Rogier W Sanders[SUP] 2 5 [/SUP], Teunis B H Geijtenbeek[SUP] 1 [/SUP]
Affiliations
Abstract
The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans, and transmitted the virus to ACE2-positive cells. Notably, human primary nasal cells were infected by SARS-CoV-2 and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.
Keywords: Heparan sulfate proteoglycans; SARS-CoV-2; dendritic cells; epithelial cells; low molecular weight heparins.
. 2021 Sep 12;e106765.
doi: 10.15252/embj.2020106765. Online ahead of print.
Infection and transmission of SARS-CoV-2 depends on heparan sulfate proteoglycans
Marta Bermejo-Jambrina[SUP] 1 [/SUP], Julia Eder[SUP] 1 [/SUP], Tanja M Kaptein[SUP] 1 [/SUP], John L van Hamme[SUP] 1 [/SUP], Leanne C Helgers[SUP] 1 [/SUP], Killian E Vlaming[SUP] 1 [/SUP], Philip J M Brouwer[SUP] 2 [/SUP], Ad C van Nuenen[SUP] 1 [/SUP], Marcel Spaargaren[SUP] 3 [/SUP], Godelieve J de Bree[SUP] 4 [/SUP], Bernadien M Nijmeijer[SUP] 1 [/SUP], Neeltje A Kootstra[SUP] 1 [/SUP], Marit J van Gils[SUP] 2 [/SUP], Rogier W Sanders[SUP] 2 5 [/SUP], Teunis B H Geijtenbeek[SUP] 1 [/SUP]
Affiliations
- PMID: 34510494
- DOI: 10.15252/embj.2020106765
Abstract
The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans, and transmitted the virus to ACE2-positive cells. Notably, human primary nasal cells were infected by SARS-CoV-2 and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.
Keywords: Heparan sulfate proteoglycans; SARS-CoV-2; dendritic cells; epithelial cells; low molecular weight heparins.