Immunopathology in Lungs after Intranasal Challenge with Live Virus in EHV-1 Recovered Murine Model of EHV-1 Infection: Lessons Learned From Unexpected Findings

Abstract

Equine herpes virus (EHV-1) causes wide-spread infection among horses worldwide. Virus causes respiratory disease, abortion, neonatal death, paresis, retinopathy, viramea and becomes latent. Horses show transient immunity after EHV-1 infection, where immune responses have been observed to decline after a few months of infection and recovered horses are prone to EHV-1 reinfection. Due to transient immune responses, effective and lasting vaccination to EHV-1 remains a challenge. In an HSV murine model, mice provides solid protection and recovered mice could not be re-infected. In this study we infected mice with EHV-1 intra nasally and after five months, mice were re-infected with EHV-1 along with the previously placebo control. It was expected that mice that had recovered would show some level of protection, but in fact they showed unexpectedly severe clinical signs and more deaths on reinfection. Reinfected mice showed severe breathing difficulties, abdominal breathing, weight loss and death compared to mice infected for the first time. The answers to the worst clinical signs came from post-mortem and histopathological findings. Lungs of challenged mice showed severe consolidation and profound infiltration of inflammatory cells such that the normal parenchyma and architecture of lungs were completely lost. The results of this study suggest that immunoreactive pathological mechanisms exists and should be considered in designing intranasal vaccine preparation for EHV-1 and possibly for other respiratory infections.