# PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue

## TL;DR

This study shows how pseudorabies virus causes neurological damage in mice by triggering inflammation and cell death through a specific signaling pathway.

## Contribution

The study reveals a novel mechanism of PRV-induced neuroinflammation involving the NF-κB/MLKL pathway and necroptosis.

## Key findings

- PRV infection activates the NF-κB/MLKL pathway, leading to neuroinflammatory injury.
- Necroptosis contributes to brain tissue damage during PRV infection.
- Inhibiting MLKL with NSA reduces inflammation and cell death in infected mice and cells.

## Abstract

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.