2. Academic Validation
  3. S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity

S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity

  • Dev Cell. 2021 Oct 25;56(20):2790-2807.e8. doi: 10.1016/j.devcel.2021.09.016.
Francisco S Mesquita 1,  Laurence Abrami 2,  Oksana Sergeeva 2,  Priscilla Turelli 2,  Enya Qing 3,  Béatrice Kunz 2,  Charlène Raclot 2,  Jonathan Paz Montoya 4,  Luciano A Abriata 4,  Tom Gallagher 3,  Matteo Dal Peraro 4,  Didier Trono 2,  Giovanni D'Angelo 4,  F Gisou van der Goot 5
Affiliations

Affiliations

  • 1 Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland. Electronic address: francisco.mesquita@epfl.ch.
  • 2 Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
  • 3 Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL, USA.
  • 4 Institute of Bioengineering, School of Life Sciences, EPFL, Lausanne, Switzerland.
  • 5 Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland. Electronic address: gisou.vandergoot@epfl.ch.
PMID: 34599882 DOI: 10.1016/j.devcel.2021.09.016
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.

Keywords

S-palmitoylation; SARS; ZDHHC; coronavirus; lipid microdomains; lipid sorting; spike; viral envelope; virus.

Figures