细胞凋亡在猪伪狂犬病毒变异株致宿主胸腺损伤中的作用与机制

The epidemic of pseudorabies (PR) caused by porcine pseudorabies virus (PRV) variant strains has resulted in serious economic losses to the pig industry in China. However, the pathogenesis of PRV variants remains unclear, and the mechanisms of the host immune response against PRV variants infection was also poorly understood. In this study, the role and underlying mechanisms of cell apoptosis in thymus injury of host infected with PRV variants will be revealed by using animal infection experiment, immunohistochemistry, confocal and other methods. Procedure of this study was designed as the following: firstly, why PRV variants infection inducing the severe atrophy of host thymus and the role of cell apoptosis in the process were investigated; secondly, the cell apoptosis in the host thymus post-infected with PRV variants was detected, the types of apoptotic cells and infected thymic cells was identified, and then the relationship between them was illustrated; thirdly, the main pathway of PRV variants infection inducing cell apoptosis of host thymus was explored and its underlying mechanism was investigated. In short, this study will systematically investigate the role of cell apoptosis in thymus injury of host infected with PRV variants and study its underlying mechanisms in vitro and in vivo, based on morphology and immunology, and from the cell level to molecular level. This has important significance for further elucidating the pathogenesis of PRV variants and effective prevention and control of PR.

伪狂犬病毒（PRV）变异株的流行给我国养猪业造成了严重的经济损失。目前对于PRV变异株的致病机理仍不清楚，对宿主抗PRV的免疫应答机制也知之甚少。本研究拟通过动物感染试验，采用免疫组化、confocal等方法开展细胞凋亡在PRV变异株致宿主胸腺严重损伤中的作用与机制研究：首先，研究PRV变异株感染造成宿主胸腺严重损伤的原因及细胞凋亡在此过程中可能发挥的作用；其次，研究PRV变异株感染诱导宿主胸腺内细胞凋亡情况，并对胸腺中的病毒感染细胞与凋亡细胞的种类进行鉴定，进而明确它们之间的相互关系；再次，研究PRV变异株感染诱导宿主胸腺内细胞发生凋亡的主要途径，探讨PRV变异株致宿主胸腺损伤内在机制。总之，上述内容将从分子水平到细胞水平、从形态学和免疫学及从体内和体外等方面系统研究细胞凋亡在PRV变异株致宿主胸腺损伤中的作用与机制，这对于进一步阐明PRV变异株的致病机理及PR的有效防治均具有重要意义。

伪狂犬病毒（PRV）变异株的流行给我国养猪业造成了严重的经济损失，但目前对于PRV变异株的致病机理仍不清楚。本项目研究表明细胞凋亡在PRV变异株（Fujian-LY）致感染宿主胸腺严重的病理损伤过程中起重要作用，证实PRV变异株感染引起宿主胸腺内大量细胞凋亡，尤其是胸腺皮质区内凋亡细胞数量较多，且淋巴细胞呈空泡化的部位为发生细胞凋亡的主要区域。另外，通过对PRV变异株感染宿主胸腺中的凋亡细胞种类进行研究，发现胸腺内有部分淋巴细胞能被PRV感染。进一步研究证实PRV变异株感染能显著诱导宿主胸腺内常见凋亡相关因子FasL、Fas 、Caspase-8、Caspase-3 mRNA 和蛋白表达水平提高，以及Caspase-8、Caspase-3蛋白酶活性增强，通过活化细胞凋亡的外源性途径，诱导宿主胸腺内细胞发生凋亡。本研究取得的成果为我们更加深入地了解PRV变异株的致病机理提供了新依据，为猪伪狂犬病的有效防治提供了新方向。