A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response

Camille Normand (1, 2) , Côme Thieulent (3, 4) , Christine Fortier (1, 2, 5) , Gabrielle Sutton (6, 7) , Catherine Sénamaud-Beaufort (8) , Laurent Jourdren (8) , Corinne Blugeon (8) , Pierre-Olivier Vidalain (9) , Stéphane Pronost (2, 5, 1) , Erika Hue (1, 2, 5)

1 LABÉO - LABÉO, Pôle d’analyses et de recherche de Normandie
2 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
3 Louisiana Animal Disease Diagnostic Laboratory [Baton Rouge, LA, USA]
4 Department of Pathobiological Sciences, School of Veterinary Medicine
5 ImpedanCELL
6 Cytokines and Adaptive Immunity Lab, Sainte-Justine University Hospital and Research Center, Montréal
7 UdeM - Université de Montréal
8 Genomique ENS - GenomiqueENS
9 CIRI-VIRIMI - Infection virale, métabolisme et immunité - Viral Infection, Metabolism and Immunity [CIRI]

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.

Mots clés: real-time cell assay; xCELLigence; antiviral; equid herpesvirus4; EHV-4; decitabine; horse; Equus caballus

Domaines: Médecine vétérinaire et santé animale

Camille Normand, Côme Thieulent, Christine Fortier, Gabrielle Sutton, Catherine Sénamaud-Beaufort, et al.. A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response. Viruses, 2024, 16 (5), pp.746. ⟨10.3390/v16050746⟩. ⟨hal-04574212⟩