Journal
EMERGING MICROBES & INFECTIONS
Volume 10, Issue 1, Pages 1065-1076Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2021.1932607
Keywords
SARS-CoV-2; hypoxia; ACE2; heparan sulfate; syndecan-1
Categories
Funding
- SPRI I+D COVID-19 fund (Basque Government, bG-COVID-19)
- European Research Council (ERC) [ERC-2018-StG 804236-NEXTGEN-IO, ERC-2017-AdG 788143-RECGLYCANMR]
- Severo Ochoa Excellence Accreditation from MCIU [SEV-2016-0644]
- FERO Foundation
- Juan de la Cierva-Formacion [FJC2018-035449-I, FJCI-2017-34099, FJC2019-039983-I]
- AECC Bizkaia Scientific Foundation [PRDVZ19003BOSC]
- Basque Government [48-AF-W1-2019-00012, PRE_2019_1_0320]
- La Caixa Inphinit [LCF/BQ/DR20/11790022]
- MINECO [BFU2016-76872-R]
- Excellence Networks [SAF2017-90794-REDT]
- Ramon y Cajal [RYC2018-024183-I]
- Proyectos I+D+I [PID2019-107956RA-I00]
- Ikerbasque Research Associate
Ask authors/readers for more resources
Hypoxia decreases the attachment of SARS-CoV-2 virus to epithelial cells, inhibiting the infection rate; furthermore, hypoxia affects the binding of spike protein to cells by reducing the cell surface HS levels; hypoxia or loss of HS-related proteins can reduce the binding of the virus to host cells.
A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1 alpha-dependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signalling pathway might offer therapeutic opportunities for the treatment of COVID-19.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available