Pseudorabies Virus Triggers Ferritinophagy-Mediated Ferroptosis and Neuroinflammation

A recent study published in the Proceedings of the National Academy of Sciences (PNAS) elucidates the molecular mechanisms underlying neurological damage caused by the Pseudorabies virus (PRV). PRV is an emerging zoonotic pathogen known to invade the central nervous system, leading to severe viral encephalitis. While the clinical manifestations are well-documented, the specific pathways driving neuronal injury have remained largely unclear. This research identifies that PRV infection triggers ferritinophagy, a selective form of autophagy that degrades ferritin, resulting in iron accumulation within cells. This process subsequently induces ferroptosis, an iron-dependent form of regulated cell death, and exacerbates neuroinflammation. These findings provide critical insights into the pathogenesis of PRV-induced encephalitis, highlighting the interplay between viral infection, iron metabolism, and inflammatory responses. By uncovering these mechanisms, the study opens new avenues for potential therapeutic interventions targeting ferroptosis and neuroinflammation to mitigate neurological damage in affected individuals and animals.