How SARS-CoV-2 Alters the Regulation of Gene Expression in Infected Cells.
Fiche publication
Date publication
mars 2023
Journal
The journal of physical chemistry letters
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GRANDEMANGE Stéphanie
Tous les auteurs :
Bignon E, Grandemange S, Dumont E, Monari A
Lien Pubmed
Résumé
Nonstructural accessory proteins in viruses play a key role in hijacking the basic cellular mechanisms, which is essential to promote the virus survival and evasion of the immune system. The immonuglobulin-like open reading frame 8 (ORF8) protein expressed by SARS-CoV-2 accumulates in the nucleus and may influence the regulation of the gene expression in infected cells. In this contribution, by using microsecond time-scale all-atom molecular dynamics simulations, we unravel the structural bases behind the epigenetic action of ORF8. In particular, we highlight how the protein is able to form stable aggregates with DNA through a histone tail-like motif, and how this interaction is influenced by post-translational modifications, such as acetylation and methylation, which are known epigenetic markers in histones. Our work not only clarifies the molecular mechanisms behind the perturbation of the epigenetic regulation caused by the viral infection but also offers an unusual perspective which may foster the development of original antivirals.
Référence
J Phys Chem Lett. 2023 03 27;:3199-3207