SARS-CoV-2 nucleocapsid protein hijacks host transcription by targeting eEF1A1.

Authors

Baptiste Bidon, Yu-Lin Lai, Tai-Ling Chao, Gawa Chen, Yee-Shin Lee, Hsiang-Hung Huang, Jia-Syuan Chen, Alejandro Gonzalez Losada, Sui-Yuan Chang, Jean-Marc Egly, Tsai-Kun Li

Published in

Life science alliance. Volume 9. Issue 12. Epub Oct 14, 2026.

Abstract

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.

PMID:
42875173
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.