ECSIT在VISA信号复合物组装及细胞抗病毒反应中的作用机制研究

线粒体和VISA信号复合物在细胞抗病毒天然免疫反应过程中发挥着十分关键的作用。病毒感染细胞之后，RIG-I/MDA5被招募到线粒体并与VISA发生相互作用，从而促进VISA信号复合物的组装，诱导I型干扰素的表达。RIG-I的活化和VISA信号复合物的组装过程受到了严格而又精细地调控。在我们的前期研究中，我们发现线粒体蛋白ECSIT能够介导RIG-I和VISA的相互作用，从而促进病毒诱导的I型干扰素表达与细胞的抗病毒天然免疫反应。本项目将从ECIST在 VISA信号复合物的组装过程中的重要功能入手，深入研究RIG-I活化和VISA信号复合物组装的调控机制，以及线粒体蛋白在这个过程中的重要功能。该项目的成功完成，不仅对阐述RIG-I样信号转导过程及其精细调控机制作出贡献，而且对线粒体蛋白在细胞抗病毒信号转导过程中的重要调控作用提供新的范例。

RIG-I and MDA5 specifically detect viral RNAs that are produced during viral infection and replication. Binding of RIG-I/MDA5 to viral RNA leads to recruitment of a downstream adaptor protein VISA which localized on mitochondrial outer membrane. VISA acts as a crucial adapter for assembling a virus-induced complex on the mitochondrial that signals IFNs activation. However, the components of the VISA-associated complex and their roles in antiviral response are not fully understood yet. In this project, we found that ECST regulated the activation of the RLRs and assemble of the VISA-associated complex, which is crucial for IFNs induction. This study contributes to the elucidation of complicated molecular mechanisms of innate immune responses, and provides new evidences that the mitochondrial proteins participated in the regulation of the cellular antiviral response.