Metabolomic evidence of bovine leukemia virus regulation on ferroptosis in bovine mammary epithelial cells.

Bovine leukemia virus (BLV) is a globally prevalent pathogen that can cause enzootic bovine leukosis (EBL), which reduces dairy cows' immunity, interferes with mammary antimicrobial defense capabilities, and exacerbates clinical mastitis. However, the specific mechanisms by which these effects occur remain incompletely understood. Ferroptosis, an iron-dependent non-apoptotic cell death mechanism, exhibits dual roles in viral infections. In this study, wild-type BLV and a miRNA-deficient mutant strain (BLV-ΔmiRNA) were used to infect bovine mammary epithelial cells in vitro, combined with non-targeted metabolomics to investigate BLV-regulated ferroptosis evidence. The results shown that BLV significantly elevated levels of unsaturated fatty acid, interferes with vitamin B6 metabolism. Suggest that BLV promote ferroptosis in mammary epithelial cells through unsaturated fatty acid biosynthesis and vitamin B6 metabolism pathways, potentially involving BLV-encoded miRNAs. This research provides a theoretical foundation for identifying novel BLV pathogenic targets and prevention strategies.