PRV Induces Neurological Inflammatory Injury by Activating Necroptosis of Brain Tissue

Area of Science:

• Virology
• Neuroscience
• Immunology

Background:

• Pseudorabies virus (PRV) causes significant economic losses in the pork industry and neurological disease in various species.
• Mechanisms of PRV-induced neuroinflammation and necroptosis are not well understood.
• Previous studies show PRV infects murine neuronal cells and activates the NF-κB/MLKL pathway.

Purpose of the Study:

• To investigate the mechanisms of PRV-induced neuroinflammatory injury and necroptosis.
• To evaluate the role of the NF-κB/MLKL pathway in PRV-induced neurological damage.
• To assess the therapeutic potential of targeting necroptosis in PRV infection.

Main Methods:

• Kunming mice and mouse astrocytes (C8-D1A) were infected with PRV-GXLB-2013 at varying doses.
• Neurological injury, inflammatory responses, and pathological changes were evaluated.
• A selective MLKL inhibitor, necrosulfonamide (NSA), was used to block necroptosis.

Main Results:

• Higher PRV doses in mice led to increased mortality, severe neurological symptoms, and brain inflammation.
• PRV infection upregulated inflammatory cytokines and NF-κB/MLKL pathway components in astrocytes.
• NSA treatment significantly reduced PRV-induced inflammation, mitochondrial damage, and necrosis.

Conclusions:

• PRV infection triggers neuroinflammatory injury via necroptosis activation and the NF-κB/MLKL signaling pathway.
• Necroptosis plays a critical role in PRV-induced neurological damage.
• Targeting necroptosis may offer a therapeutic strategy for PRV-induced neurological disease.