SARS-CoV-2 nucleocapsid protein hijacks host transcription by targeting eEF1A1.
8 affiliations
- 1Taiwan International Bio Research Center (TIBRC), College of Medicine, National Taiwan University, Taipei, Taiwan.
- 2Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
- 3Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- 4Department of Life Science, Institute of Ecology and Evolutionary Biology, National Taiwan University, Taipei, Taiwan.
- 5Cell Biology and Pharmacogenomics Department, PharmaMar S.A, Colmenar Viejo, Spain.
- 6Taiwan International Bio Research Center (TIBRC), College of Medicine, National Taiwan University, Taipei, Taiwan [email protected].
- 7Institut de Génétique, Biologie Moléculaire et Cellulaire, Strasbourg (IGBMC), Université de Strasbourg, Strasbourg, France.
- 8Development Center for Biotechnology, Taipei, Taiwan.
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.
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BibTeX
@article{bidon2026sarscov2,
title = {{SARS-CoV-2 nucleocapsid protein hijacks host transcription by targeting eEF1A1.}},
author = {Baptiste Bidon and Yu-Lin Lai and Tai-Ling Chao and Gawa Chen and Yee-Shin Lee and Hsiang-Hung Huang and Jia-Syuan Chen and Alejandro Gonzalez Losada and Sui-Yuan Chang and Jean-Marc Egly and Tsai-Kun Li},
journal = {Life science alliance},
year = {2026},
month = oct,
doi = {10.26508/lsa.202603751},
url = {https://europepmc.org/article/MED/42875173},
note = {CC BY},
}
RIS
TY - JOUR
TI - SARS-CoV-2 nucleocapsid protein hijacks host transcription by targeting eEF1A1.
AU - Baptiste Bidon
AU - Yu-Lin Lai
AU - Tai-Ling Chao
AU - Gawa Chen
AU - Yee-Shin Lee
AU - Hsiang-Hung Huang
AU - Jia-Syuan Chen
AU - Alejandro Gonzalez Losada
AU - Sui-Yuan Chang
AU - Jean-Marc Egly
AU - Tsai-Kun Li
PY - 2026
DA - 2026/10/14
JO - Life science alliance
DO - 10.26508/lsa.202603751
UR - https://europepmc.org/article/MED/42875173
AB - 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.
SN - 2575-1077
ER -