African Swine Fever Virus DP71L Protein Inhibits Dextran Sulfate Sodium (DSS)-Induced Murine Colitis

The functions of most proteins encoded by the African swine fever virus (ASFV) remain largely unknown, although several have been reported to possess immunomodulatory properties. Among these, we identified that the DP71L protein exerts an inhibitory effect on inflammatory bowel disease. To investigate its protective role in murine colitis, we constructed and expressed a recombinant DP71L protein. Colitis was induced in mice using DSS, and the effects of DP71L treatment were evaluated by assessing histopathological changes, inflammatory cytokine profiles, oxidative stress markers, colonic tissue pathology, and the expression of tight-junction proteins (claudin-1, occludin, and ZO-1). Our results showed that DP71L intervention significantly attenuated body weight loss and organ damage and ameliorated DSS-induced colonic histopathological injury. Moreover, DP71L treatment markedly increased superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) content in colonic tissues. Mechanistically, DP71L suppressed both DSS-induced NF-κB and JAK-STAT activation and concurrently inhibited DSS-induced epithelial cell apoptosis. These events likely underlie the observed reduction in pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, and TNF-α) and the restoration of tight-junction protein expression, as DP71L treatment effectively prevented DSS-induced downregulation of claudin-1, occludin, and ZO-1, while also promoting the anti-inflammatory cytokines IL-10 and TGF-β. Collectively, our findings demonstrate that DP71L effectively inhibits the progression of murine colitis through coordinated anti-inflammatory and anti-apoptotic mechanisms. This study suggests that DP71L may function as a potential immunosuppressant, opening new avenues for the application of viral proteins in the treatment of immune-related disorders.