单纯疱疹病毒（HSV-1）是广为流行的病毒，在人群中感染率高达90%。初次感染后病毒以潜伏态存在于三叉神经元（TG）中，其间断性再发感染导致黏膜溃疡，若感染角膜，则罹患致盲的病毒性基质角膜炎（HSV-1 Stromal Keratitis， HSK），严重影响患者生活质量。HSV-1如何在潜伏态和裂解态的不断转换中逃逸机体的免疫监视一直是未解之谜。我们近期发现HSV-1能够直接感染T细胞，并通过阻断T细胞受体激活的信号通路，抑制T细胞的活性。由此我们提出假设“HSV-1感染并抑制T细胞而逃逸宿主免疫监视”。本项目将探究HSV抑制T细胞活化的分子机制，寻找和确定HSV-1蛋白与宿主T细胞中的靶蛋白相互结合的作用位点，了解HSV对TG驻留T细胞的影响，并建立HSV-T细胞相互作用机制与病毒逃逸宿主免疫反应的内在关系，为更好地了解疱疹病毒再发及其致病机制、控制疾病发生提供新的理论依据和治疗思路。

Herpes Simplex Virus (HSV-1) is a prevalent human pathogen carried by nearly 90% population. Upon primary infection, HSV-1 establishes lifelong latency in trigeminal ganglion neurons (TG). Periodic reactivation of HSV-1 causes recurrent lesions in mucous epithelium, including cornea that leads to HSV-1 stromal keratitis (HSK), a common cause of blindness. It remains unveiled how the virus intermittently switches between latent and lytic status under host immune surveillance. Our recently finding suggested that HSV-1 infects and suppresses T cell activation by blocking TCR-stimulated signal transduction. In this proposal, we aim to identify the viral proteins responsible for the inhibition of TCR signaling; and to investigate the effect of HSV-1 reactivation on TG residential T cells. This study will provide insights into the pathogenesis of herpes virus related diseases (such as HSK), and lead to the development of better preventive and therapeutic strategies.