RIG-I-MAVS介导的信号转导通路在细胞响应病毒侵染的天然免疫应答过程中发挥重要作用。RIG-I诱导接头蛋白MAVS形成类似于朊病毒的聚集体，进而激活下游信号通路，最终诱导I型干扰素的产生从而抑制病毒的增殖。MAVS形成聚集体进而被激活的过程不依赖于蛋白质翻译后的修饰及其表达水平的调节，因此MAVS的聚集必然存在精确的调控。在宿主细胞中过表达MAVS引起其自动激活, 并且原核表达的MAVS可以自发地形成有活性的聚集体；另一方面，在没有病毒感染条件下，宿主细胞中的MAVS始终保持非聚集且无活性的状态，表明存在有阻止MAVS自发聚集的机制。在静息条件下，细胞对MAVS的这种抑制和调控十分重要，否则持续活化的MAVS会产生过量的干扰素和促炎因子，对机体造成免疫性损伤。本项目拟在生理条件下探索MAVS保持非聚集状态的分子机制，该项目将为研究细胞天然免疫信号转导通路的复杂调控网络提供新的思路。

Innate immunity serves as the first line of host defense against invading pathogens. In response to virus infection, RIG-I senses viral RNA and activates the adaptor protein MAVS, which then forms prion-like filaments to stimulate a specific signaling pathway leading to type I interferon production to restrict virus proliferation. MAVS aggregation does not involve posttranslational modification and expression fluctuation, which must be precisely regulated. Recombinant MAVS form function aggregates spontaneously while quiescent MAVS remain a monomeric form in host cells, suggesting a mechanism preventing its spontaneous aggregation. This mechanism is crucial for the homeostasis of antiviral signaling pathway in resting cells to avoid unexpected production of inflammatory cytotines, which would be detrimental. We propose to study the very molecular mechanism keeping MAVS from accidental aggregation in host cells, thus provide insight for the sophisticated regulatory network of RIG-I-MAVS-mediated antiviral signaling and diagnostic applications for relevant autoimmune diseases.