Abstract

Pseudorabies virus (PRV), a neurotropic pathogen causing severe neurological injury in livestock, and T-2 toxin (T-2), a potent trichothecene mycotoxin associated with immunosuppression, organ toxicity, and neurotoxicity, frequently coexist in agricultural environments. However, their combined effects on brain function remain poorly understood. This study investigated whether co-exposure to T-2 and PRV produces synergistic neurotoxicity and explored the underlying mechanisms. Mice were administered low-dose T-2 (0.4 mg/kg BW) by oral gavage, followed by intramuscular PRV infection (0.1 mL of 1.0 × 10 3 TCID 50 ). Combined exposure markedly aggravated brain pathology, including increased brain volume, cerebrospinal fluid accumulation, endothelial abnormalities, and capillary congestion. Histopathological analysis revealed more pronounced neuronal degeneration and inflammation in co-exposed mice. qPCR results demonstrated that T-2 significantly enhanced PRV replication in brain tissues, suggesting that T-2 may promote viral invasion by compromising blood–brain barrier integrity. PRV infection activated the NF-κB pathway, elevating IL-6 , IL-1β , and TNF-α expression, while T-2 further amplified these inflammatory responses. In addition, co-exposure induced substantial oxidative stress, characterized by downregulation of key antioxidant genes including Nrf2 , GPX-1 , GPX-2 , CAT and SOD . In conclusion, co-exposure to T-2 and PRV exerts synergistic neurotoxic effects in mice through enhanced viral replication, intensified neuroinflammation, and impaired antioxidant defenses. These findings highlight the potential toxicological risks posed by simultaneous exposure to mycotoxins and neurotropic viruses in agricultural settings.