Peng Chunzi, Zhang Jinwu, Wu Changxu, Liu Danning, Liang Jing, Lv Maojie, Yang Shisen, Li Xiaoning, Wei Yingyi, Chen Hailan, He Jiakang, Hu Tingjun, Yu Meiling
Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China.
Microorganisms. 2025 Jun 30;13(7):1531. doi: 10.3390/microorganisms13071531.
Pseudorabies virus (PRV) can infect a wide range of animal species, including swine and rodents. Infection in pigs is associated with significant economic losses in the global pork industry and is characterized by acute, often fatal disease, as well as central nervous system (CNS) invasion, which leads to neurological manifestations. Although PRV replication has been extensively characterized in certain murine neuronal cell lines such as Neuro-2a, the mechanisms underlying PRV-induced neuroinflammatory injury and necroptosis remain largely unclear. In this study, Kunming mice and mouse astrocytes (C8-D1A) were infected with PRV-GXLB-2013 at different doses to evaluate neurological injury and inflammatory responses. Given that the NF-κB/MLKL signaling pathway was found to be activated during PRV infection, a selective MLKL inhibitor, necrosulfonamide (NSA), was applied to investigate the role of necroptosis in PRV-induced neuroinflammatory damage. Mice infected with higher viral doses showed increased mortality, severe neurological symptoms, elevated brain inflammation, and pathological changes. In C8-D1A cells, PRV infection significantly upregulated inflammatory cytokines and key components of the NF-κB/MLKL pathway. Importantly, NSA treatment markedly reduced these inflammatory responses, mitochondrial damage, and cellular necrosis. Collectively, these findings suggest that PRV infection triggers neuroinflammatory injury through the activation of necroptosis and the NF-κB/MLKL signaling pathway. This study provides novel mechanistic insights into PRV-induced neurological damage and highlights potential therapeutic targets for intervention.
伪狂犬病病毒（PRV）可感染包括猪和啮齿动物在内的多种动物物种。猪感染该病毒会给全球猪肉产业带来重大经济损失，其特征为急性、常致命的疾病，以及中枢神经系统（CNS）侵袭，进而导致神经症状。尽管PRV在某些小鼠神经元细胞系（如Neuro-2a）中的复制已得到广泛研究，但PRV诱导神经炎性损伤和坏死性凋亡的机制仍 largely不清楚。在本研究中，用不同剂量的PRV-GXLB-2013感染昆明小鼠和小鼠星形胶质细胞（C8-D1A），以评估神经损伤和炎症反应。鉴于发现NF-κB/MLKL信号通路在PRV感染期间被激活，应用选择性MLKL抑制剂坏死磺酰胺（NSA）来研究坏死性凋亡在PRV诱导的神经炎性损伤中的作用。感染较高病毒剂量的小鼠死亡率增加、出现严重神经症状、脑炎症升高和病理变化。在C8-D1A细胞中，PRV感染显著上调炎性细胞因子和NF-κB/MLKL通路的关键成分。重要的是，NSA治疗显著降低了这些炎症反应、线粒体损伤和细胞坏死。总体而言，这些发现表明PRV感染通过激活坏死性凋亡和NF-κB/MLKL信号通路引发神经炎性损伤。本研究为PRV诱导的神经损伤提供了新的机制见解，并突出了潜在的干预治疗靶点。
