亲环素A对RLR介导的抗病毒天然免疫的调控机制

亲环素A（Cyclophilin A，CypA）是一种肽基脯氨酰顺/反异构酶，在细胞的生命活动中起着许多重要作用。CypA能够与某些病毒蛋白相互作用而影响病毒的复制，但CypA如何通过调控宿主的天然免疫来影响病毒的复制，我们却知之甚少。我们的前期研究发现CypA能够增强仙台、流感、水泡性口炎病毒感染的293T细胞中IFN-β的产生。进一步研究表明，CypA能够通过增强IRF3的磷酸化来增强IFN-β的产生，并且CypA可以与RLR信号通路中的RIG-I/MDA5相互作用，但其调控机理尚不清楚。本项目拟利用CypA敲除的293T细胞和来源于CypA敲除小鼠的巨噬细胞和鼠胚成纤维细胞，深入揭示CypA在RLR通路的作用靶点和作用机理，同时检测CypA对小鼠抗病毒能力的影响，从而阐明CypA对RLR介导的抗病毒天然免疫的调控机制。本研究有助于深入了解CypA在宿主抗病毒天然免疫防御系统中的作用。

Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase with many biological functions. Recently, it has been reported CypA could inhibit virus replication by interacting with viral proteins.However,whether CypA is involved in regualtion of host antiviral immunity is largely unknown.Our recent studies indicated that CypA could increase type I interferon production induced by the infection of several viruses, such as sendai virus, vesicular stomatitis virus and influenza virus in 293T cells. Further study showed CypA regulated virus-induced interferon by enhancing IRF3 phosphorylation.We also observed CypA could interact with RLR signaling pathway components RIG-I and MDA5, but the regulation mechanism is still unclear. In this proposal, we will further investigate the mechanism of how CypA regulates RLR-mediated immune response by using both CypA knockout 293T cell and CypA-deficient macrophage from CypA knockout mice. We will also evaluate the antiviral effect of CypA during early viral infection in vivo in murine model. We hope our study will provide insights of the roles of CypA in host antiviral innate immunity.