Infection and transmission of SARS-CoV-2 depends on heparan sulfate proteoglycans

Autor: Killian E Vlaming, Godelieve J. de Bree, John L. van Hamme, Julia Eder, Marcel Spaargaren, Teunis B. H. Geijtenbeek, Neeltje A. Kootstra, Marta Bermejo-Jambrina, Tanja M. Kaptein, Frank E.H.P. van Baarle, Philip J. M. Brouwer, Leanne C. Helgers, Bernadien M. Nijmeijer, Rogier W. Sanders, Marit J. van Gils, Alexander P.J. Vlaar
Rok vydání: 2020
Předmět:
DOI: 10.1101/2020.08.18.255810
Popis: 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. Moreover, 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.
Databáze: OpenAIRE