Abstract
Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the “old mare model” to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMCs) of horses prior to infection and during viremia were collected and RNA sequencing with differential gene expression was used to compare the transcriptome of horses that did (EHM group) and did not (non-EHM group) develop clinical EHM. Interestingly, horses exhibiting EHM did not show respiratory disease, while non-EHM horses showed significant respiratory disease starting on day 2 post infection. Multiple immune pathways differed in EHM horses in response to EHV-1. These included an upregulation of IL-6 gene expression, a dysregulation of T-cell activation through AP-1 and responses skewed towards a T-helper 2 phenotype. Further, a dysregulation of coagulation and an upregulation of elements in the progesterone response were observed in EHM horses.
Highlights
All horses were free from clinical signs of respiratory disease, had normal body temperatures, and were negative for Equine herpesvirus-1 (EHV-1) genome in nasal swab and Peripheral blood mononuclear cells (PBMCs) samples when tested by real-time PCR prior to challenge infection (CH) with EHV-1
This approach was based on the fact that equine herpesvirus myeloencephalopathy (EHM) typically only occurs sporadically in EHV-1 infected horses and is challenging to induce experimentally [19]
Our goal was to take advantage of this phenomenon and use RNA sequencing to analyze the transcriptomic profile of PBMCs in horses that did and did not develop
Summary
It is the cause of upper respiratory disease, late term abortion or the crippling neurologic disease equine herpesvirus myeloencephalopathy (EHM). In a recent U.S outbreak, as many as 14% of infected animals died or were euthanized due to EHM and to date, no vaccine is effective in preventing EHM [2,3]. This means strict biosecurity and quarantines during an outbreak remain the most effective strategy to control losses due to EHM. In order to limit these devastating consequences, the current recommendation is that state animal health officials issue quarantines of premises with EHV-1 confirmed cases for 21 days from the onset of the last case of EHM [4]
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