INTRODUCTION: The large yellow croaker iridovirus (LYCIV) poses a significant threat to the aquaculture industry of METHODS: In this study, an epigenetic approach was employed to investigate dynamic changes in chromatin accessibility using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Additionally, RNA sequencing (RNA-seq) was used to analyze the expression pattern of immune response genes upon LYCIV infection. RESULTS: Substantial alterations in chromatin accessibility were observed, particularly in the regulatory regions of key immune-related genes. Significant changes in the expression of AP-1 transcription factors, including the DISCUSSION: These findings suggest that AP-1 may play a crucial role in the defense response against viral infection by modulating inflammatory cytokines and contributing to cellular inflammatory responses. This study provides a comprehensive analysis of the epigenomic landscape and gene expression regulation during iridovirus infection in