S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity.
Dev Cell
; 56(20): 2790-2807.e8, 2021 10 25.
Article
in En
| MEDLINE
| ID: mdl-34599882
ABSTRACT
SARS-CoV-2 virions are surrounded by a lipid bilayer that contains membrane proteins such as spike, responsible for target-cell binding and virus fusion. We found that during SARS-CoV-2 infection, spike becomes lipid modified, through the sequential action of the S-acyltransferases ZDHHC20 and 9. Particularly striking is the rapid acylation of spike on 10 cytosolic cysteines within the ER and Golgi. Using a combination of computational, lipidomics, and biochemical approaches, we show that this massive lipidation controls spike biogenesis and degradation, and drives the formation of localized ordered cholesterol and sphingolipid-rich lipid nanodomains in the early Golgi, where viral budding occurs. Finally, S-acylation of spike allows the formation of viruses with enhanced fusion capacity. Our study points toward S-acylating enzymes and lipid biosynthesis enzymes as novel therapeutic anti-viral targets.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acylation
/
SARS-CoV-2
/
COVID-19 Drug Treatment
/
Membrane Lipids
Limits:
Humans
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2021
Document type:
Article