A screening study identified decitabine as an inhibitor of Varicellovirus equidalpha4 that enhances the innate antiviral response - Archive ouverte HAL
Communication Dans Un Congrès Année : 2024

A screening study identified decitabine as an inhibitor of Varicellovirus equidalpha4 that enhances the innate antiviral response

Catherine Sénamaud-Beaufort
Laurent Jourdren
Corinne Blugeon

Résumé

Background: Varicellovirus equidalpha4 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 alpha EHV infection still constitutes an important threat to the horse industry. Objectives : Testing the efficacy of different compounds on EHV-4 and studying the mode of action of the most effective one Study Design Screening and transcriptomic approach Methods: 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 (xCELLigence and videomicroscopy) and the viral load was quantified by qPCR. Results: Potential antiviral activities were confirmed for 8 molecules from the 42 compounds (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine is the most potent compound against EHV-4 in vitro with an EC50 value of 1.16 ± 0.31 µM and 0.28 ± 0.05 µM measured by xCELLigence and by qPCR, respectively. A transcriptomic analysis revealed an increase of expression of various genes involved in the interferon response. Main Limitations: Study performed on one cell line with one reference strain Conclusions: This work confirms the effect of ganciclovir against EHV-4 in vitro. Our study was unable to demonstrate in vitro the antiviral activity of aciclovir against EHV-4, a molecule frequently used in the field by veterinary practitioners against equine herpesviruses. The compound with the best efficacy in inhibiting EHV-4 replication in vitro is decitabine. Transcriptomic analysis of infected cells treated with decitabine revealed activation of the innate antiviral response by stimulation of the interferon pathway.
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Dates et versions

hal-04651833 , version 1 (17-07-2024)

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  • HAL Id : hal-04651833 , version 1

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Camille Normand, Christine Fortier, Côme Thieulent, Gabrielle Sutton, Catherine Sénamaud-Beaufort, et al.. A screening study identified decitabine as an inhibitor of Varicellovirus equidalpha4 that enhances the innate antiviral response. XIIe journée scientifique de l’association HerPAs, Association Herpas herpesvirus et pathologies associées, Jun 2024, Tours, France. ⟨hal-04651833⟩
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