TRIM家族蛋白中许多成员是重要的干扰素刺激因子，在宿主的抗病毒天然免疫反应中扮演着重要作用。目前发现TRIM15蛋白可调控IFN-β的产生，但其具体分子细节并不清楚。我们通过串联亲和纯化技术发现TRIM15与宿主蛋白酮戊二酸脱氢酶（OGDH）存在相互作用，而且下调内源性OGDH表达后能增强仙台病毒诱导的IFN-β产生，但OGDH在TRIM15抗病毒天然免疫中功能及其分子机制需要进一步深入研究。本研究拟以TRIM15与OGDH蛋白相互作用为切入点，利用蛋白质质谱、蛋白互作、超表达、siRNA干扰、荧光素酶报告系统等方法和技术研究：（1）TRIM15与OGDH蛋白互作分子细节及其对OGDH表达与修饰的影响；（2）OGDH蛋白对IFN-β信号通路的调控作用；（3）TRIM15与OGDH互作在其调控IFN-β信号通路中功能与机制。该研究为进一步揭示TRIM15抗病毒天然免疫调控机制提供科学依据。

Most members of TRIM (Tripartite motif) family of proteins are recognized as the products of interferon-stimulated genes (ISGs) and as immune signaling mediators. Various TRIM proteins mediate antiviral response and play a very important role in innate antiviral immunity. Studies showed that TRIM15 was a critical component of the RLR signaling and could positively regulate the production of interferon beta (IFN-β), but the molecular mechanism still keeps unclear. Our previous study had identified the interaction between TRIM15 and oxoglutarate dehydrogenase (OGDH). We also found that knockdown of OGDH enhanced Sendai virus-induced IFN-β production. However, further research is required to be done to elucidate the function and molecular mechanism of the interaction between OGDG and TRIM15 in regulating innate antiviral immunity. In this project, TRIM15 and OGDG will be studied by the methods of protein mass spectrometry technology, protein-protein interaction, proteins overexpression, siRNA knockdown, plaque forming unit test and Dual-luciferase assay. We hope to address the following questions: (1).The interaction between TRIM15 and OGDH, and the influence on the expression and post-translational modifications of OGDH by TRIM15; (2). The role of OGDH in the production of type I interferon (IFN-β) pathway; (3). The function and molecular mechanism to active the IFN-β signal pathways and its relevance to the interaction between TRIM15 and OGDH. This study will be useful to clarity the mechanism of TRIM15-mediated regulation of innate antiviral immunity, and contribute to the understanding of immune regulation and develop antiviral drug to some infectious disease in the future.