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

• DOI: 10.1016/j.virs.2024.01.002
• Publication Date: 2024-01-18T07:37:47Z
• Authors: Wei Yang; Chong-Yang Tang; Dong-Ying Fan; Yi-Song Wang; Pei-Gang Wang; Jing An; Guo-Ming Luan
• Keywords: Mice, Knockout; Epilepsy; Brain; Herpes Simplex; Herpesvirus 1, Human; Receptor, Interferon alpha-beta; Mice, Inbred C57BL; Mice; Disease Models, Animal; Interferon Type I; Animals; Female; Encephalitis, Herpes Simplex; Protein Interaction Maps; Research Article; Signal Transduction

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/β receptor (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.