Abstract
Since 2016, the novel variant infectious bursal disease virus (nVarIBDV) has emerged as the predominant strain in China, which characterized by causing subclinical but persistent immunosuppression and substantial economic losses in chickens. However, the global transcriptomic changes and regulatory mechanisms in the bursa of Fabricius (BF) during nVarIBDV infection remain unclear. In this study, transcriptome sequencing of BF from infected chickens identified 5,775 differentially expressed mRNAs (DEmRNAs), 535 lncRNAs (DElncRNAs), and 1,072 circRNAs (DEcircRNAs) at 7 days post-infection (dpi), along with 5,275 DEmRNAs at 14 dpi. Functional enrichment analysis showed these genes were involved in immune and inflammatory responses, such as NF-kappa B signaling, cytokine-cytokine receptor interaction, T cell activation, and extracellular matrix remodeling. Protein-protein interaction networks highlighted hub genes related to antiviral response (e.g., CD4, IFN-γ, GZMA), T cell exhaustion (e.g., CTLA-4, LAG3, PD-L1), and fibrosis (e.g., COL1A1, MMP9). Notably, key B-cell-related genes (BTK, RAG2, SYK) were significantly down-regulated, indicating impaired humoral immunity. Competing endogenous RNA (ceRNA) network analysis suggested that DElncRNAs and DEcircRNAs may act as miRNA sponges, regulating genes in Hippo, Ras, and cAMP pathways. RT-qPCR validation of 20 differentially expressed genes (DEGs) confirmed the RNA-seq reliability. This study reveals a dynamic host response involving immune activation, T cell exhaustion, B-cell depletion, and maladaptive tissue repair, offering the first comprehensive transcriptomic landscape of chicken BF during nVarIBDV infection and insights into its immunosuppressive mechanisms.