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

• Published in: Virologica Sinica Vol. 39; no. 2; pp. 251 - 263
• Main Authors: Yang, Wei, Tang, Chong-Yang, Fan, Dong-Ying, Wang, Yi-Song, Wang, Pei-Gang, An, Jing, Luan, Guo-Ming
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2024; KeAi Publishing Communications Ltd; Wuhan Institute of Virology, Chinese Academy of Sciences
• Subjects: Animal models; Animals; Atrophy; Brain - pathology; Brain - virology; Chronic infection; Disease Models, Animal; Drug resistance; Encephalitis; Encephalitis, Herpes Simplex - immunology; Encephalitis, Herpes Simplex - pathology; Encephalitis, Herpes Simplex - virology; Epilepsy; Epilepsy - pathology; Epilepsy - virology; Epstein-Barr virus; Female; Gene expression; Gene set enrichment analysis; Genes; Herpes simplex; Herpes Simplex - immunology; Herpes Simplex - pathology; Herpes Simplex - virology; Herpes viruses; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - pathogenicity; Human herpes viruses (HHVs); IFN-I signaling; Infections; Interferon; Interferon Type I - immunology; Interferon Type I - metabolism; Laboratory animals; Lesions; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurological disorders; Protein Interaction Maps; Proteins; Public health; Rasmussen's encephalitis (RE); Receptor, Interferon alpha-beta - deficiency; Receptor, Interferon alpha-beta - genetics; Signal Transduction; Traumatic brain injury; Viral infections; Beijing China; China; IFN-I signaling; Human herpes viruses (HHVs); Rasmussen's encephalitis (RE)
• ISSN: 1995-820X; 1674-0769; 1995-820X
• DOI: 10.1016/j.virs.2024.01.002

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. •Mice with IFN-I signaling deficiency are prone to HSV-1 induced epilepsy.•Repression of IFN-I signaling promotes brain atrophy in RE and other HHVs encephalitis.•Intact IFN-I signaling significantly restricts HHVs-induced neural symptoms.