单疱病毒性角膜炎（HSK）是由HSV-1感染角膜引发的严重致盲性眼病。病毒原发感染后终生潜伏在三叉神经节内，反复复发引起角膜病变，目前对HSV-1潜伏复发的机制仍不清楚。我们前期的研究发现：Substance P（SP）在HSV-1感染角膜后的三叉神经节内大量释放，潜伏期仍维持较高水平；在体外，SP可活化三叉神经节细胞中的Akt信号，促进HSV-1的潜伏并抑制其复发，阻断SP信号则会诱导HSV-1复发，同时SP可促进神经细胞的存活。以上提示SP是调控HSV-1在三叉神经节内潜伏复发的关键。基于此，本项目拟通过HSV-1潜伏感染的神经细胞模型和HSK小鼠模型，并结合SP缺陷小鼠，深入研究SP诱导并维持HSV-1在三叉神经节内潜伏和抑制其复发的关键作用，阐明SP信号通路调控HSV-1潜伏复发的分子机制，并初步探讨利用SP衍生短肽防治HSK复发的可行性，为HSK的临床治疗提供新的靶标和干预策略。

Herpes simplex keratitis (HSK) is a severe blinding eye disease caused by HSV-1. After primary infection, HSV-1 enters trigeminal ganglion (TG) for lasting latency, and leads to keratopathy through repeated recurrence, however, the mechanism of latency and recurrence is not clear until now. From the previous studies, we found that substance P (SP) was released from the TG after HSV-1 infection in cornea, and still maintained a relative higher level during latency. We also found that SP could activate Akt signaling in TG cells in vitro, promote HSV-1 latency and inhibit its reactivation; blocking SP induced HSV-1 reactivation; meanwhile, SP could promote TG cell survival. These suggested SP is a key factor to regulate HSV-1 latency and recurrence in TG. Based on the above findings, here we will further explore the key roles of SP inducing and maintaining HSV-1 latency, inhibiting its recurrence in TG, and illuminate the molecular mechanism of SP signaling pathway in regulation of HSV-1 latency and recurrence in TG, by using HSV-1 latent infection model in TG cells, HSK mouse model, and combined with the SP knock-out mouse. We will also evaluate the feasibility of using SP derived peptide for prophylaxis and treatment of recurrent HSK. The purpose of this study is to enrich the knowledge of neuropeptide involved in virus-host interaction theory, and provide the novel target and strategy for the clinical HSK therapy.