Mutidi-mensional pathogenicity characterization with emphasis on intestinal dysfunction mechanism of two circulating Chinese field strains of feline panleukopenia virus.

Feline panleukopenia virus (FPV) causes severe, highly contagious infectious diseases in domestic cats, yet the comprehensive pathogenic mechanisms of circulating field isolates remain incompletely elucidated. Here, two contemporary FPV field strains (F513 and F1105) were isolated and genetically characterized from clinical samples of FPV vaccinated diarrheic cats. In vivo pathogenicity assays demonstrated that both strains induced typical FPV clinical signs, with viral replication predominantly localized to the gastrointestinal tract and shedding primarily occurring via the fecal-oral route. Both isolates triggered robust, time-dependent humoral immune responses and progressive systemic oxidative stress in infected cats. Notably, FPV infection profoundly reshaped the feline intestinal microbiota, characterized by reduced microbial diversity, depleted beneficial commensals, and expanded potential pathogens. Histopathological analyses revealed that strain F513 induced more severe systemic necrotizing inflammatory lesions than F1105, accompanied by higher viral antigen loads in all examined tissues. Mechanistically, FPV infection significantly downregulated intestinal tight junction proteins (Claudin-1, Occludin, ZO-1), while upregulating myosin light chain kinase (MLCK) and the epithelial-mesenchymal transition (EMT) marker N-cadherin, thereby compromising intestinal epithelial barrier integrity. Collectively, these findings clarify the multi-dimensional pathogenic characteristics of FPV field strains and reveal a critical role for intestinal barrier dysfunction in FPV pathogenesis, providing novel insights for therapeutic target development and disease prevention.