TY - JOUR
T1 - Infection and transmission of SARS-CoV-2 depend on heparan sulfate proteoglycans
AU - Bermejo-Jambrina, Marta
AU - Eder, Julia
AU - Kaptein, Tanja M.
AU - van Hamme, John L.
AU - Helgers, Leanne C.
AU - Vlaming, Killian E.
AU - Brouwer, Philip J. M.
AU - van Nuenen, Ad C.
AU - Spaargaren, Marcel
AU - de Bree, Godelieve J.
AU - Nijmeijer, Bernadien M.
AU - Kootstra, Neeltje A.
AU - van Gils, Marit J.
AU - Sanders, Rogier W.
AU - Geijtenbeek, Teunis B. H.
N1 - Funding Information: We thank Jonne Snitselaar and Yoann Aldon for help with production of antibodies and Hildo Lantermans for help with the XG1/EXT1 KO cell lines. This research was funded by the Netherlands Organisation for Health Research and Development (ZonMw) together with the Stichting Proefdiervrij (ZonMw MKMD COVID‐19 grant nr. 114025008 to TBHG), ZonMw (446002508 to GJB) and European Research Council (Advanced grant 670424 to TBHG), Amsterdam UMC PhD grant and two COVID‐19 grants from the Amsterdam institute for Infection & Immunity (to TBHG, RWS, and MJG). This study was also supported by the Netherlands Organization for Scientific Research (NWO) through a Vici grant (to RWS), and by the Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD), grant INV‐002022 (to RWS). Publisher Copyright: © 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license
PY - 2021/10/18
Y1 - 2021/10/18
N2 - 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.
AB - 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.
KW - Heparan sulfate proteoglycans
KW - SARS-CoV-2
KW - dendritic cells
KW - epithelial cells
KW - low molecular weight heparins
UR - http://www.scopus.com/inward/record.url?scp=85115296235&partnerID=8YFLogxK
U2 - https://doi.org/10.15252/embj.2020106765
DO - https://doi.org/10.15252/embj.2020106765
M3 - Article
C2 - 34510494
SN - 0261-4189
VL - 40
JO - EMBO Journal
JF - EMBO Journal
IS - 20
M1 - e106765
ER -