RETRACTED ARTICLE: Astrocyte-derived MMP-9 is a key mediator of pseudorabies virus penetration of the blood–brain barrier and tight junction disruption

Year: 2025

Type: article

Abstract: Pseudorabies virus (PRV) infection leads to viral encephalitis and neurological damage in mice, causing significant neurological symptoms and brain damage. This study aimed to investigate the cellular mechanisms of PRV-induced encephalopathy and the role of matrix metalloproteinase-9 (MMP-9) in blood-brain barrier (BBB) disruption. We found that PRV infection increased the number of astrocytes and induced a phenotypic shift from the A2 to the A1 subtype, which was associated with increased secretion of MMP-9. MMP-9 was identified as a critical mediator of PRV-induced BBB disruption, as it degrades collagen VI, leading to BBB damage. PRV was shown to penetrate the BBB via a paracellular pathway, and MMP-9 deletion reversed this damage, mitigating tight junction injury. Additionally, PRV infection caused an "inflammatory storm" in the central nervous system (CNS), with increased levels of the chemokines CCL-3, CCL-4, and CCL-5; the cytokines IL-6 and IL-18; and TNF-α. The expression of INF-γ was significantly decreased. In conclusion, PRV infection disrupts the BBB and induces an inflammatory response in the CNS, with MMP-9 playing a key role in mediating BBB damage. These findings provide insights into the pathogenesis of PRV-induced encephalopathy and potential therapeutic targets for viral encephalitis.

Source: Veterinary Research

DOI: 10.1186/s13567-025-01486-z