MEK/ERK-Mediated Transcriptional Repression of Metabolic Genes Confers Host Defense Against Gallid alphaherpesvirus 1 Infection via Modulating Fos Nuclear Translocation

Infectious laryngotracheitis virus (ILTV), formally known as Gallid alphaherpesvirus 1, represents a prominent alphaherpesvirus that poses a significant threat to the global poultry industry. Current routine vaccination strategies fail to eliminate latent infection. Host–pathogen interaction networks have become a key focus in antiviral research. Our previous study demonstrated that activation of the MEK/ERK signaling pathway upon ILTV infection restricts host cellular metabolic activity to mount protective host antiviral responses, yet the underlying molecular mechanism remains unclear. The present work systematically dissects the contribution of MEK/ERK signaling to intrinsic host defense against ILTV. The results show that ILTV infection activates the MEK/ERK pathway, which in turn promotes the expression, activation, and nuclear translocation of the transcription factor Fos. As a core transcriptional regulator, Fos represses host metabolic gene expression, thereby restricting viral replication and proliferation. Integrated multi-omics analyses further demonstrate that the MEK/ERK-Fos-metabolic regulatory axis operates uniformly during infection with avian, human, and porcine alphaherpesviruses, suggesting a broadly conserved host antiviral mechanism. This consistent cross species signaling pattern points toward an evolutionarily conserved host antiviral strategy and provides potential molecular targets for the development of broad-spectrum antiviral strategies against alphaherpesviruses.