CMV致病性及疾病转归与宿主免疫状态密切相关。CMV dsDNA被免疫识别并诱导的天然免疫变化是影响感染结局的第一个"道闸"。我们前期研究发现HCMV以poly(dA:dT)相同方式激活巨噬细胞的AIM2炎性体，提出天然免疫细胞内能识别外源性dsDNA的AIM2炎性体通路是"桥接"抗CMV天然免疫和获得性免疫的关键环节。本项目将在细胞水平研究AIM2炎性体通路在抗HCMV免疫应答中的作用与调控机制，通过选择性阻断技术反向寻找其关键作用位点；借助MCMV急性感染(C57BL/6)和慢性感染(BALB/c)的基因敲除小鼠模型和骨髓重建技术，整体研究AIM2炎性体通路启动和调控抗CMV天然与获得性免疫应答的作用与机制及其对抗病毒效应与感染结局的影响；进一步体外研究HCMV抑制AIM2炎性体通路而实现免疫逃逸的相关蛋白分子及其作用机制，将有助于全面阐明CMV免疫致病机制和免疫逃逸与感染慢性化机制。

The pathogenicity of CMV and the prognosis of CMV diseases are closely related to the host immune status. CMV dsDNA was recognized by innate immune cells, which induced the change of innate immunity was the first "switch" affecting the outcome of the CMV infections. Our previous studies found that HCMV could activate the AIM2 inflammasome of the microphages as the same way as poly (dA:dT). We so supposed that AIM2 inflammasome pathway which recognizes the exogenous dsDNA in innate immune cells plays a key role of linking between the innate and acquired immune against CMV. This project means to: (1) in HCMV infected macrophage model, study the role and regulatory mechanisms of AIM2 inflammasome pathway in the anti-HCMV immune responses, and find reversely out the key target component of AIM2 inflammasome pathway affected by HCMV using selective siRNA interfering and specific inhibitor techniques in vitro; (2) by means of the MCMV acute (C57BL/6) and chronic (BALB/c) infected gene-knock-out (AIM2-/- or caspase-1-/-) mice models and bone marrow reconstitution techniques, investigate the role and mechanisms of AIM2 inflammasome pathway on triggering and regulating the innate and acquired immunity against CMV by assessing the responses of anti-MCMV immunity and the outcome of infections in vivo; (3) further explore the related protein of HCMV restraining the AIM2 inflammasome pathway and its mechanisms in vitro. All of these will contribute to comprehensively elucidate the mechanisms of immune pathogenesis, immune escape and chronicity of CMV infection.