Equine herpesvirus 1 (EHV1) is a ubiquitous and highly contagious pathogen that causes a range of disease severity from mild rhinopneumonitis to abortion, neurologic disease, and death. Notable outbreaks in recent years have emphasized the potential virulence of EHV1, the limitations of current vaccines, and ensuing economic impacts. The broad objective of this research is to identify treatments that will 1) significantly decrease EHV1 viral load, and consequent pathology and shedding during lytic infection; 2) complement antiviral drug efficacy during EHV1 infection; and 3) inhibit EHV1 reactivation from latency. The immediate objective of this project is to evaluate the potential of epigenetic drugs to modulate EHV1 infection because EHV1 gene expression is regulated by epigenetic mechanisms, primarily through histone modifications. Sustaining a repressive epigenetic state through inhibition of histone demethylation has been shown to effectively limit human a-herpesviruses in vitro and in vivo^1-3. This outcome was observed both during lytic infection and reactivation from latency. Our hypothesis is that maintaining a repressive epigenetic state on the EHV1 genome will decrease viral load during lytic infection, and prevent reactivation from latency. Thus, we propose the following specific aims using in vitro systems:

Aim 1) to determine how histone demethylase inhibition decreases EHV1 viral load and gene expression during lytic infection;

Aim 2) to determine how histone demethylase inhibition decreases EHV1 reactivation from latently infected cells;

Aim 3) to determine the epigenetic state of the EHV1 genome in the presence or absence of histone demethylase inhibition.