Whole-transcriptome analysis of BLV-infected cows reveals downregulation of immune response genes in high proviral loads cows

Bovine leukemia virus (BLV) is a retrovirus that infects cattle, causing bovine enzootic leukosis, a chronic disease characterized by the proliferation of infected B cells. BLV proviral load (PVL) is a key determinant of disease progression and transmission risk. Cattle can exhibit distinct phenotypes of low PVL (LPVL) or high PVL (HPVL), which remain stable throughout their lifetime. Differential expression analysis revealed 1,908 differentially expressed genes (DEGs) between HPVL and LPVL animals, including 774 downregulated (DReg) and 1,134 upregulated (UReg) genes. Functional enrichment analysis revealed that DReg genes were associated primarily with immune response pathways. Conversely, the UReg genes were enriched in processes related to cell cycle regulation, mitotic division, and DNA biosynthesis. Protein-protein interaction analysis revealed six highly interconnected clusters. Interestingly, a cluster was enriched for sphingolipid metabolism, a process critical to enveloped virus infection and immune receptor signaling. These findings provide valuable insights into the molecular mechanisms of BLV infection, suggesting potential markers for disease monitoring and targets for therapeutic intervention.