A screening study identified decitabine as an inhibitor of Equid Herpesvirus 4 that enhances the innate antiviral response

Equid herpesvirus 4 (EHV-4) is a frequent respiratory pathogen of the horse. EHV-4 sporadically induces abortion or neonatal death and although not clearly demonstrated its involvement in neurological forms is strongly suspected. Despite preventive treatments using vaccines against EHV-1/EHV-4, the resurgence of a-EHV infection still constitutes an important threat to the horse industry. Yet very few studies have been conducted on the search for antiviral molecules against EHV-4. A screening of 42 antiviral compounds was performed in vitro on E. Derm cells infected with EHV-4 405/76 reference strain (VR2230). Formation of cytopathic effects was monitored by Real-Time Cell Analysis (RTCA) and the viral load was quantified by qPCR. Aciclovir, the most widely used antiviral in vivo against alpha-herpesviruses, does not appear to be effective against EHV-4 in vitro. Potential antiviral activities were confirmed for 8 molecules (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine is the most potent compound against EHV-4 in vitro. A transcriptomic analysis revealed an increase of expression of different genes implicated in IFN response. Decitabine (DTB) seems to activate the immune antiviral pathway. Overall design: Comparison of gene expression in dermal horse cells after 18 hours for cells infected or not with EHV-4 virus and/or treated with decitabine