Mice with type I interferon signaling deficiency are prone to epilepsy upon HSV-1 infection

Viral encephalitis continues to be a significant public health concern.In our previous study,we discovered a lower expression of antiviral factors,such as IFN-β,STING and IFI16,in the brain tissues of patients with Rasmussen's encephalitis(RE),a rare chronic neurological disorder often occurred in children,characterized by unihemispheric brain atrophy.Furthermore,a higher cumulative viral score of human herpes viruses(HHVs)was also found to have a significant positive correlation with the unihemispheric atrophy in RE.Type I IFNs(IFN-I)signaling is essential for innate anti-infection response by binding to IFN-α/βreceptor(IFNAR).In this study,we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1(HSV-1)via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions.While all mice exhibited typical viral encephalitis lesions in their brains,HSV-induced epilepsy was only observed in A6 mice.The gene expression matrix,functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy.Additionally,ten key genes with the highest scores were identified.Taken together,these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions,thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.