Infection and transmission of SARS-CoV-2 depend on heparan sulfate proteoglycans.
Marta Bermejo-JambrinaJulia EderTanja M KapteinJohn L van HammeLeanne C HelgersKillian E VlamingPhilip J M BrouwerAd C van NuenenMarcel SpaargarenGodelieve J de BreeBernadien M NijmeijerNeeltje A KootstraMarit J van GilsRogier W SandersTeunis B H GeijtenbeekPublished in: The EMBO journal (2021)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- dendritic cells
- induced apoptosis
- cell cycle arrest
- endothelial cells
- coronavirus disease
- machine learning
- immune response
- gene expression
- regulatory t cells
- big data
- genome wide
- endoplasmic reticulum stress
- signaling pathway
- electronic health record
- oxidative stress
- deep learning
- replacement therapy
- angiotensin converting enzyme
- angiotensin ii
- chronic rhinosinusitis