天然免疫反应是机体抵抗病原体入侵、保护自身的第一道防线，随着研究的深入发现p53在病毒侵染机体触发免疫系统产生免疫防御应答过程中发挥着关键性作用。我们发现在免疫应答过程中p53显著促进IRF7的转录表达。然而病毒在进化过程中通过编码多功能蛋白，一方面调控病毒自身复制，另一方面通过特定病毒蛋白逃逸或抑制宿主抗病毒天然免疫反应。我们发现NL63编码的木瓜样蛋白酶PLP2 能明显下调宿主细胞中的p53蛋白水平，而且能明显抑制poly(I-C)刺激所引起的IFN-β的转录激活以及细胞凋亡，从而抵抗宿主细胞的免疫应答。基于以上工作我们拟将深入研究p53在宿主细胞抵抗病毒感染的先天免疫调控中的新功能及其作用机制，并且探索病毒蛋白PLP2与p53之间的调控关系以及PLP2在抵抗宿主抗病毒天然免疫反应中的作用机制。本研究不仅具有重要的科学意义，而且将为病毒的临床治疗与预防提供重要的参考。

The natural immune response is the first line of the body to resist pathogen invasion. p53 plays a crucial role in the immune defense response process when virus infects the body to trigger the immune system. We found that p53 significantly promotes the transcription of IRF7 gene in the immune response. However, virus generally encodes the multifunctional proteins which regulate virus proliferation or inhibit the host antiviral innate immune response. PLP protein which encoded by coronavirus is the recently discovered multifunctional protease. We found that protease PLP2 encoded by NL63 markedly decreases p53 protein levels in the host cell, and can significantly inhibit the IFN-beta transcriptional activation and apoptosis stimulated by poly (I:C), and then resists the immune response of the host cell. Based on the above work, we intend to explore the new features of p53 in the field of immune regulation as well as the studies of the coronavirus protein PLP2 on the regulation of p53 immune function. This study will have important scientific significance, and might provide novel insights into the clinical treatment and prevention.