Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate.
Emerg Microbes Infect
; 10(1): 1065-1076, 2021 Dec.
Article
in English
| MEDLINE | ID: covidwho-1236184
ABSTRACT
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-1α-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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cell Hypoxia
/
Neuropilin-1
/
Syndecan-1
/
Spike Glycoprotein, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
Heparitin Sulfate
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Emerg Microbes Infect
Year:
2021
Document Type:
Article
Affiliation country:
22221751.2021.1932607
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