生物钟调控单纯疱疹病毒性脑炎及作用机制研究

单纯疱疹病毒性脑炎（HSE）是由I型单纯疱疹病毒（HSV-1）诱导的严重中枢神经系统疾病。在无有效治疗的情况下，HSE可导致患者死亡。阿昔洛韦是临床上治疗HSE的一线药物，但长期使用易造成病毒耐药。因此亟待开发更有效更安全的HSE治疗药物。生物钟参与调节生物节律、病毒感染和炎症反应等多种生理行为。在前期工作中，我们发现HSV-1感染的严重程度以及病毒宿主受体Nectin-1的表达受生物钟调节，且时钟因子REV-ERBα会影响Nectin-1基因、病毒基因及蛋白的表达水平。然而，REV-ERBα调控Nectin-1并影响HSV-1感染的机制尚不明确。本项目拟在前期基础上，探究REV-ERBα通过调控Nectin-1影响HSV-1感染的机制，并探讨REV-ERBα配体对HSE的治疗作用。项目的实施将阐明生物钟调控HSV-1感染和HSE的作用机制，为抗HSV-1感染和HSE的治疗提供新靶点。

Herpes simplex virus encephalitis (HSE) is a serious central nervous system disease induced by herpes simplex virus type 1 (HSV-1). In the absence of effective treatment, HSE can cause death. Acyclovir is the first-line drug for the clinical treatment of HSE, but long-term acyclovir treatment can lead to HSV-1 drug resistance. Therefore, it is urgent to develop more effective and safer HSE treatment drugs. The circadian clock system is involved in regulating biological rhythms, viral infections, inflammatory responses and other physiological behaviors. In the previous work, we found that the severity of HSV-1 infection and the expression of the viral host receptor Nectin-1 were regulated by the circadian clock, and the circadian clock factor REV-ERBα affected the expression levels of Nectin-1, viral genes and proteins. However, the mechanism by which REV-ERBα regulates Nectin-1 and affects HSV-1 infection remains unclear. This project intends to explore the mechanism by which REV-ERBα affects HSV-1 infection through regulation of Nectin-1, and explore the therapeutic effect of REV-ERBα ligands on HSE. The implementation of this project will clarify the mechanism of the circadian clock regulating HSV-1 infection and HSE, and provide novel targets for the treatment of HSV-1 infection and HSE.