Infection and transmission of SARS-CoV-2 depend on heparan sulfate proteoglycans
Marta Bermejo-Jambrina, Julia Eder, Tanja M Kaptein, John L van Hamme, Leanne C Helgers, Killian E Vlaming, Philip J M Brouwer, Ad C van Nuenen, Marcel Spaargaren, Godelieve J de Bree, Bernadien M Nijmeijer, Neeltje A Kootstra, Marit J van Gils, Rogier W Sanders, Teunis B H Geijtenbeek, Marta Bermejo-Jambrina, Julia Eder, Tanja M Kaptein, John L van Hamme, Leanne C Helgers, Killian E Vlaming, Philip J M Brouwer, Ad C van Nuenen, Marcel Spaargaren, Godelieve J de Bree, Bernadien M Nijmeijer, Neeltje A Kootstra, Marit J van Gils, Rogier W Sanders, Teunis B H Geijtenbeek
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.
Conflict of interest statement
The authors declare that they have no conflict of interest.
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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