伪狂犬病毒（Pseudorabies virus, PRV）变异株已成为我国猪群中的主要流行毒株。与经典株相比，PRV变异株感染猪的病理变化以多器官坏死性炎症为主要特征，但其具体机制仍不清楚。课题组前期发现，PRV变异株感染可引起细胞坏死和MLKL分子磷酸化。程序性坏死是最新发现的一种受RIPK1/RIPK3/MLKL级联调控的细胞死亡方式，我们相信它很可能与PRV变异株诱导的坏死性炎症有关。鉴于此，我们拟以PRV变异株感染猪肾上皮细胞PK-15，利用透射电镜、激光共聚焦等技术对细胞微观形态、功能分子互作进行研究，揭示PRV变异株感染对程序性坏死的调控作用及分子机制；通过药物干预与基因沉默等手段抑制通路关键分子进行反向研究，明确程序性坏死在病毒胞内复制与胞外释放等感染过程中的作用。进一步的，通过对PRV变异株感染猪局部组织器官的综合检测，分析程序性坏死在PRV变异株诱导坏死性炎症中的作用。

At present, the variant strain of Pseudorabies virus (PRV) has become the main epidemic strain in piglets in China. Compared with the classical strain, pigs infected by PRV variant strains are characterized by the pathology of the necrotizing inflammatory, while the mechanism of it is not clarified. In the previous study, we found that PRV variant strains induced necrotic cell death and the phosphorylation of MLKL. Necroptosis is a recently reported cell death manner which is regulated by the cascade reaction of RIPK1, RIPK3 and MLKL. We believe that it is likely to be involved in the necrotic progress of cells and the necrotizing inflammatory response during PRV variant strains infection. Hence, further research will be performed in this project. PRV variant strains will be utilized to infect porcine kidney cells PK-15. By using electron microscopy and confocal immunofluorescence microscopy, cell micromorphology and the interaction of functional molecules will be analyzed to explore the mechanism of necroptosis in cells infected by PRV variant strains. Taking advantage of drug interference and gene silence, we will perform the reverse research to confirm the role of necroptosis in intracellular replication and extracellular release during PRV variant strains infection. Further, the role of necroptosis in the necrotizing inflammatory was analyzed by a comprehensive study of tissues and organs in pigs infected by PRV variant strains.