单疱病毒6B型（HHV-6B）和单疱病毒7型（HHV7）感染是难治性颞叶内侧癫痫的重要病因之一，但其致痫机制尚不清楚。目前研究显示自噬在病毒复制激活和免疫异常中发挥关键作用，而TLR4信号通路是自噬核心调控因子。课题组前期研究证实HHV-6B/HHV-7与颞叶内侧癫痫相关且患者存在免疫异常，发现患者海马自噬激活现象且其与标志HHV-6B病毒早期感染的外壳蛋白表达直接相关，TLR4表达上调，因此提出TLR4诱导自噬激活HHV-6B/HHV-7复制活化最终致痫假说。本项目拟在前期研究基础上，结合体内和离体实验，应用透射电镜、海马脑片培养、神经细胞培养、膜片钳和免疫印迹等技术探索TLR4诱导自噬信号转导通路的具体作用途径，并给予TLR4阻断，观察干预TLR4-自噬对病毒复制激活、免疫因子表达及海马神经元兴奋性的影响。本研究完成有助于明确HHV-6B/HHV-7感染所致难治性颞叶内侧癫痫病理机制。

HHV-6B and HHV-7 virus infection is an important etiologic factor of resistent mesial temporal lobe epilepsy(MTLE) but the mechanism is not clear. In our previous studies, HHV6B and HHV-7 were verified as etiologic factors of resistent meisial temporal lobe epilepsy. We found autophagy activating in neurol cells of hippocampus from patients with HHV6B infection, and it is associated with the epression of virul proteins which represent early infection. We also found the expression of TLR4, a key factor which regulate autophagy was up-reglated. We hypothesize that the role of autophagy regulated by TLR4 plays an important role in resistent MTLE due to HHV-6B/HHV-7 infection. We plan to use technology including electron microscopy, hippocampus slice cultivation, CNS nerve cell culture patch clamp and western blot etc to explore the conrect pathway of TLR4 singal way. We also use TLR4 blocker to investigate the role of TLR4-induced-autophagy in virus replication, activation, immune factors expression and impact of hippocampus excity. The study aim to explore the mechanism of resistent MTLE induced by HHV6B/7 infection. We try to find a new way to investigate MTLE due to HHV6B/HHV-7 infection.