Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice.
Authors: Mesquita Leonardo P, Costa Rafael C, Mesquita Laís L R, Lara Maria do Carmo C S H, Villalobos Eliana M C, Mori Claudia M C, Mori Enio, Howerth Elizabeth W, Maiorka Paulo C
Journal: Veterinary pathology
Summary
# Editorial Summary: EHV-1 Neurovirulence in a Murine Model Two neurovirulent equid alphaherpesvirus 1 (EHV-1) strains—A4/72 and A9/92—were intranasally inoculated into C57BL/6J mice to characterise the central nervous system pathology and inflammatory mechanisms underlying EHV-1 myeloencephalopathy, a significant neurological complication in horses. By day 3 post-inoculation, infected mice developed severe neurological signs accompanied by extensive viral replication within neurons and surrounding tissue, alongside prominent liquefactive necrosis, microglial activation, and perivascular infiltration of T cells and macrophages particularly in the olfactory bulb and ventral brain regions. The researchers identified moderate expression of the chemokines CCL5 and CCL2 in neuroglial cells at infection sites, plus widespread caspase-3 activation indicating programmed cell death across both severely and mildly affected brain areas. These findings suggest that EHV-1-induced neurological disease involves a rapidly progressive, inflammatory cascade characterised by direct viral cytotoxicity, microglial activation, and chemokine-mediated recruitment of immune cells that may paradoxically amplify neuronal damage. For equine practitioners, this work reinforces the aggressive nature of neurological EHV-1 (herpes myeloencephalopathy) and highlights potential therapeutic targets—such as anti-inflammatory strategies or modulation of chemokine signalling—that warrant investigation as adjunctive treatments alongside antiviral therapy in naturally affected horses.
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Practical Takeaways
- •This mouse model demonstrates the mechanisms of EHV-1 neuropathology but has limited direct application to equine practice; findings are primarily relevant for researchers studying viral pathogenesis
- •Understanding chemokine and apoptosis markers in EHV-1 CNS infection may eventually inform therapeutic targets, though clinical translation remains distant
- •The study characterizes two highly neurovirulent EHV-1 strains that could be concerning if they represent field-relevant virus variants affecting horses
Key Findings
- •Two neurovirulent EHV-1 strains (A4/72 and A9/92) induced severe neurological signs in mice by 3 days post-inoculation
- •Infected mouse brains showed fulminant necrotizing lymphohistiocytic meningoencephalitis with prominent microgliosis and perivascular cuffing of T cells and macrophages
- •Neuroglial cells expressed CCL5 and CCL2 chemokines and numerous neurons expressed cleaved caspase-3, indicating apoptosis-mediated neuronal death
- •Ultrastructural analysis revealed numerous viral nucleocapsids within degenerated and necrotic neurons