Encephalomyocarditis virus (EMCV) is a potentially zoonotic virus that induces multi-systemic diseases in the host, including encephalitis, myocarditis, and reproductive disorders. The infected animals show intestinal immune imbalance and altered gut microbiota, leading to marked mucosal injury. However, currently, the host-regulated pathways and significant therapeutic strategies capable of mitigating EMCV-induced intestinal damage are not well characterized. Our previous laboratory investigations revealed that curcumol inhibited the replication of EMCV in vitro. In this study, an EMCV-infected mice model was established to evaluate the effect of curcumol on EMCV-induced intestinal damage and its impact on the gut microbiota. These effects were evaluated by qRT-PCR, Western blot, H&E staining, and 16S rDNA techniques. The results showed that curcumol treatment alleviated EMCV-induced intestinal injury in mice. Curcumol treatment increased the expression of intestinal tight junction mRNA (ZO-1, Occludin) and proteins. It also increased the abundance of Corynebacterium mastitidis and Mucispirillum schaedleri of the ileum microbiota. Further analysis revealed that in comparison to the virus group, curcumol administration markedly increased IFN-β protein expression in blood, ileum, and colon in mice. Western blot demonstrated that relative abundance of DHX15, NLRP6, and P-IRF3 proteins was elevated in different curcumol dose groups compared with that of the virus group. Therefore, our current study revealed that Curcumol treatment improved the gut microbiota, promoted IFN-β expression through the DHX15-NLRP6-IRF3 signaling pathway, and alleviated the intestinal pathologic injury induced by EMCV infection in mice.

To Cite This Article: Zhou W, Haseeb A, Zheng K, Sun N, Zhong J, Yang H, Fan K, Yin W, Sun Y, Khan A, Li H and Sun P, 2026. Curcumol inhibits EMCV-induced intestinal injury in mice by modulating the DHX15-Nlrp6-IRF3-IFN-β signaling pathway. Pak Vet J, 46(7): 1732-1742. http://dx.doi.org/10.29261/pakvetj/2026.166