Comparative screening of Amur tiger cytokines identifies IL-15 as a cytoprotective candidate against feline panleukopenia virus infection.

Comparative studies of species-derived cytokines remain limited in endangered carnivores. We cloned six immune-related cytokines from Amur tigers (Panthera tigris altaica), with sequence analysis revealing >90% identity across Felidae. Among all tested cytokines, IL-15 demonstrated superior and sustained lymphocyte-stimulatory activity at 200 ng/mL. To investigate antiviral potential, F81 cells were pretreated with IL-15 and challenged with feline panleukopenia virus (FPV). Mechanistic studies revealed that IL-15 attenuated virus-induced apoptosis by modulating key regulatory proteins: downregulating pro-apoptotic factors (Bax, Caspase3/9, p53, Cytc) while upregulating anti-apoptotic Bcl-2. Additionally, IL-15 preserved mitochondrial integrity by maintaining membrane potential, enhancing fusion proteins (MFN1/MFN2), and suppressing fission protein Drp1. IL-15 also strengthened cellular antioxidant defenses through increased SOD1/SOD2 expression, significantly reducing reactive oxygen species (ROS) accumulation. These protective effects persisted for 48 h post-infection, demonstrating sustained cytoprotective effects. These findings reveal species-specific IL-15-mediated antiviral mechanisms within the Felidae family and provide comparative insights into how immune defenses are optimized in species with constrained evolutionary history, with implications for understanding carnivore immune evolution and conservation medicine.