Fiche publication
Date publication
décembre 2026
Journal
Life science alliance
Auteurs
Membres identifiés du Cancéropôle Est :
Dr EGLY Jean-Marc
Tous les auteurs :
Bidon B, Lai YL, Chao TL, Chen G, Lee YS, Huang HH, Chen JS, Gonzalez Losada A, Chang SY, Egly JM, Li TK
Lien Pubmed
Résumé
SARS-CoV-2 variants display substantial genetic and phenotypic diversity, yet the molecular mechanisms underlying their effects on host gene regulation need further investigation. We performed a transcriptomic analysis of host responses to multiple SARS-CoV-2 variants, including Delta and Omicron. Despite their divergence, all variants induced a conserved transcriptional program in human lung epithelial cells characterized by activation of interferon regulatory factors (IRFs), immediate-early genes, and downstream cytokines. We identify the viral nucleocapsid (N) protein as a central driver of this transcriptional reprogramming, as N expression alone partially recapitulated the host response to infection. Mechanistically, N promotes recruitment of interferon regulatory factors and AP-1 transcription factors, RNA polymerase II, and the elongation factor eEF1A1 to promoters of pro-inflammatory genes, revealing a previously unrecognized nuclear role for eEF1A1. Disruption of the N-eEF1A1 interaction, genetically or pharmacologically using the eEF1A interactant plitidepsin, abolished transcriptional complex formation and reversed host gene dysregulation, identifying a conserved host-virus regulatory axis and potential pan-variant therapeutic target.
Mots clés
Humans, Peptide Elongation Factor 1, metabolism, SARS-CoV-2, genetics, Host-Pathogen Interactions, genetics, Coronavirus Nucleocapsid Proteins, metabolism, Transcription, Genetic, Gene Expression Regulation, RNA Polymerase II, metabolism, Phosphoproteins, metabolism, Epithelial Cells, metabolism, Transcription Factor AP-1, metabolism
Référence
Life Sci Alliance. 2026 12;9(12):
