PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue
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 le...
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MDPI AG
2025-06-01
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| author | Chunzi Peng Jinwu Zhang Changxu Wu Danning Liu Jing Liang Maojie Lv Shisen Yang Xiaoning Li Yingyi Wei Hailan Chen Jiakang He Tingjun Hu Meiling Yu |
| author_facet | Chunzi Peng Jinwu Zhang Changxu Wu Danning Liu Jing Liang Maojie Lv Shisen Yang Xiaoning Li Yingyi Wei Hailan Chen Jiakang He Tingjun Hu Meiling Yu |
| author_sort | Chunzi Peng |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-402b0598cf9246d89d43b9e989ddd903 |
| institution | DOAJ |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj-art-402b0598cf9246d89d43b9e989ddd9032025-08-20T02:47:09ZengMDPI AGMicroorganisms2076-26072025-06-01137153110.3390/microorganisms13071531PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain TissueChunzi Peng0Jinwu Zhang1Changxu Wu2Danning Liu3Jing Liang4Maojie Lv5Shisen Yang6Xiaoning Li7Yingyi Wei8Hailan Chen9Jiakang He10Tingjun Hu11Meiling Yu12Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaGuangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, ChinaPseudorabies 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.https://www.mdpi.com/2076-2607/13/7/1531PRV infectionneurological inflammatory injurynecroptosisNF-κB signaling pathway |
| spellingShingle | Chunzi Peng Jinwu Zhang Changxu Wu Danning Liu Jing Liang Maojie Lv Shisen Yang Xiaoning Li Yingyi Wei Hailan Chen Jiakang He Tingjun Hu Meiling Yu PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue Microorganisms PRV infection neurological inflammatory injury necroptosis NF-κB signaling pathway |
| title | PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue |
| title_full | PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue |
| title_fullStr | PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue |
| title_full_unstemmed | PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue |
| title_short | PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue |
| title_sort | prv induces neurological inflammatory injury by activating necroptosis of brain tissue |
| topic | PRV infection neurological inflammatory injury necroptosis NF-κB signaling pathway |
| url | https://www.mdpi.com/2076-2607/13/7/1531 |
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