sCD83在高致病性猪繁殖与呼吸综合征病毒调控巨噬细胞极化及活性中的作用

PRRSV感染对机体免疫细胞及细胞因子的分泌产生重大影响，从而引起猪体持续感染和免疫逃逸，给养猪业造成巨大的经济损失。CD83是树突细胞表面的重要分子，其分泌型CD83（sCD83）是少数具有免疫抑制能力的细胞因子，能作用于多种免疫细胞。前期研究表明，PRRSV感染后，可通过其功能蛋白N、Nsp1α及Nsp10的关键氨基酸位点，促进sCD83的分泌，进而发挥免疫抑制效应。本项目旨在研究sCD83在PRRSV感染过程中，对巨噬细胞极化和活性的作用及对T细胞增殖的影响，并探究其分子机制。另外，本项目拟应用感染性克隆技术构建敲除PRRSV中sCD83功能蛋白关键氨基酸位点的多种突变体重组PRRSV，比较各个突变体重组病毒诱导sCD83分泌、调控巨噬细胞极化和活性、抑制T细胞增值的能力。本项目的实施将进一步阐明并丰富PRRSV的致病机理，为该病毒新型疫苗研究以及该病防治提供新线索。

Porcine reproductive and respiratory syndrome virus (PRRSV) infection significantly impacts on generation of immune cells in the innate and adaptive immune system, manipulate the secretion of various cytokines, which suppresses the innate immune response and induces persistent infection, causing giant economic loss in the swine industry. CD83 is an important molecule on the surface of dendritic cells. Its secreted CD83(sCD83) is one of the few cytokines with immunosuppressive function, which can act on a variety of immune cells. Our previous experiments demonstrated that PRRSV infection can enhanced release of soluble CD83 through its key functional domain of nucleocapsid protein, nonstructural protein 1α(nsp1α), and nsp10, thereby exerting the effect of immunosuppression. This study aims to investigate the role of sCD83 on the polarization and activation of macrophages, the proliferation of T cells during PRRSV infection, then to explore its molecular mechanism. In addition, this project intends to use reverse genetics to construct multiple recombinant mutant PRRSV that knock out functional sites that regulate sCD83 secretion in PRRSV. Compare the ability of each mutant virus to induce the expression level of sCD83, to regulate the macrophage polarization and activity, and the effects of T cell proliferation. This research will further illuminate and enrich the pathopoiesis mechanisms of PRRSV, and provide new clues for the development of new vaccines and the prevention and treatment of PRRS.