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

作　　者：Wei Yang Chong-Yang Tang Dong-Ying Fan Yi-Song Wang Pei-Gang Wang Jing An Guo-Ming Luan 

机构地区：[1]Beijing Key Laboratory of Epilepsy,Sanbo Brain Hospital,Capital Medical University,Beijing,100093,China [2]Beijing Institute for Brain Disorders,Capital Medical University,Beijing,100093,China [3]Department of Neurosurgery,Epilepsy Center,Sanbo Brain Hospital,Capital Medical University,Beijing,100093,China [4]Department of Microbiology,School of Basic Medical Sciences,Capital Medical University,Beijing,100069,China [5]Chinese Institute for Brain Research,Beijing,102206,China

出　　处：《Virologica Sinica》2024年第2期251-263,共13页中国病毒学（英文版）

基　　金：supported by the Collaborative Research Fund of Chinese Institute for Brain Research,Beijing(No.2020-NKX-XM-02);the Capital's Funds for Health Improvement and Research(2022-1-8011);the National Natural Science Foundation of China(81790654,81790650,82241071).

摘　　要：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.

关 键 词：IFN-I signaling Human herpes viruses(HHVs) Rasmussen's encephalitis(RE) 

分 类 号：R392-33[医药卫生—免疫学]