A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response
Camille Normand,
Côme J. Thieulent,
Christine Fortier,
Gabrielle Sutton,
Catherine Senamaud-Beaufort,
Laurent Jourdren,
Corinne Blugeon,
Pierre-Olivier Vidalain,
Stéphane Pronost,
Erika S. Hue
Affiliations
Camille Normand
LABÉO, 14280 Saint-Contest, France
Côme J. Thieulent
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
Christine Fortier
LABÉO, 14280 Saint-Contest, France
Gabrielle Sutton
Cytokines and Adaptive Immunity Lab, Sainte-Justine University Hospital and Research Center, University of Montréal, Montreal, QC H3T 1C5, Canada
Catherine Senamaud-Beaufort
GenomiqueENS, Institut de Biologie de l’ENS (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France
Laurent Jourdren
GenomiqueENS, Institut de Biologie de l’ENS (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France
Corinne Blugeon
GenomiqueENS, Institut de Biologie de l’ENS (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France
Pierre-Olivier Vidalain
Team Viral Infection, Metabolism and Immunity, Centre International de Recherche en Infectiologie (CIRI), Univ Lyon, Institut National de la Santé et de la Recherche Médicale (Inserm), U1111, Centre National de la Recherche Scientifique (CNRS), UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 69007 Lyon, France
Equid herpesvirus 4 (EHV-4) is a common respiratory pathogen in horses. It sporadically induces abortion or neonatal death. Although its contribution in neurological disorders is not clearly demonstrated, there is a strong suspicion of its involvement. Despite preventive treatments using vaccines against EHV-1/EHV-4, the resurgence of alpha-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 equine fibroblast cells infected with the EHV-4 405/76 reference strain (VR2230). The formation of cytopathic effects was monitored by real-time cell analysis (RTCA), and the viral load was quantified by quantitative PCR. Aciclovir, the most widely used antiviral against alpha-herpesviruses in vivo, does not appear to be effective against EHV-4 in vitro. Potential antiviral activities were confirmed for eight molecules (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine demonstrates the highest efficacy against EHV-4 in vitro. Transcriptomic analysis revealed the up-regulation of various genes implicated in interferon (IFN) response, suggesting that decitabine triggers the immune antiviral pathway.
