tetano
Editor, Senior Moderator
Life Sci Alliance
. 2026 Oct 14;9(12):e202603751.
doi: 10.26508/lsa.202603751. Print 2026 Dec.
Baptiste Bidon 1 , Yu-Lin Lai 1 , Tai-Ling Chao 2 3 , Gawa Chen 1 , Yee-Shin Lee 1 , Hsiang-Hung Huang 1 , Jia-Syuan Chen 4 , Alejandro Gonzalez Losada 5 , Sui-Yuan Chang 2 3 , Jean-Marc Egly 6 7 , Tsai-Kun Li 1 8
Affiliations Expand
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.
. 2026 Oct 14;9(12):e202603751.
doi: 10.26508/lsa.202603751. Print 2026 Dec.
SARS-CoV-2 nucleocapsid protein hijacks host transcription by targeting eEF1A1
Baptiste Bidon 1 , Yu-Lin Lai 1 , Tai-Ling Chao 2 3 , Gawa Chen 1 , Yee-Shin Lee 1 , Hsiang-Hung Huang 1 , Jia-Syuan Chen 4 , Alejandro Gonzalez Losada 5 , Sui-Yuan Chang 2 3 , Jean-Marc Egly 6 7 , Tsai-Kun Li 1 8
Affiliations Expand
- PMID: 42875173
- DOI: 10.26508/lsa.202603751
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.