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Home / Equine Research Bank / Viruses / A Screening Study Identified Decitabine as an Inhibitor of E...
Viruses2024; 16(5); 746; doi: 10.3390/v16050746

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

Abstract: 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.
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Publication Date: 2024-05-08 PubMed ID: 38793627PubMed Central: PMC11125953DOI: 10.3390/v16050746Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research identifies decitabine as a potent inhibitor of Equid herpesvirus 4 (EHV-4), a horse respiratory pathogen, and reveals that it enhances the innate antiviral immune response in infected cells.

Background and Importance

  • Equid herpesvirus 4 (EHV-4) is a common virus affecting horses, primarily targeting the respiratory system.
  • The virus can cause serious complications such as abortion and neonatal death in horses.
  • The role of EHV-4 in causing neurological disorders is suspected but not yet clearly demonstrated.
  • Despite existing vaccines for EHV-1 and EHV-4, outbreaks of alpha-herpesvirus infections remain a serious threat to the horse industry.
  • There is a lack of research focused on finding effective antiviral drugs specifically against EHV-4.

Research Objective

  • The primary goal was to screen a panel of known antiviral compounds to identify those effective against EHV-4 in vitro.
  • The study aimed to determine if any existing antiviral drugs could inhibit viral replication and reduce cytopathic effects (cell damage caused by the virus) in equine cells.
  • Another goal was to investigate possible mechanisms by which the most effective compounds worked, particularly looking at immune responses triggered during infection.

Methods

  • In vitro screening was performed using equine fibroblast cells infected with the reference strain of EHV-4 (405/76 strain, VR2230).
  • A total of 42 antiviral compounds were tested for their ability to inhibit viral effects.
  • Real-time cell analysis (RTCA) was used to monitor the formation and extent of cytopathic effects caused by viral infection over time.
  • Quantitative PCR (qPCR) was employed to measure the viral load within the treated and untreated cells.
  • Effectiveness of the compounds was judged based on reduction in cytopathic effect and viral load.

Key Findings

  • Aciclovir, a widely used drug against alpha-herpesviruses, showed no effectiveness against EHV-4 in vitro in this study.
  • Eight antiviral molecules were identified with potential antiviral activity against EHV-4: idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine.
  • Among these, decitabine exhibited the highest efficacy in reducing viral cytopathic effects and viral load.
  • Decitabine was thus highlighted as a promising candidate for antiviral treatment against EHV-4.

Mechanism Insights from Transcriptomic Analysis

  • Gene expression analysis (transcriptomics) was performed to understand decitabine’s mode of action.
  • The analysis revealed an up-regulation of genes associated with the interferon (IFN) response pathway.
  • Interferon response is a critical part of the innate immune system, acting as the body’s first line of defense against viral infections.
  • This suggests that decitabine not only directly inhibits viral replication but also stimulates the infected cells to mount a stronger antiviral immune response.
  • The dual action of direct antiviral activity along with immune enhancement may contribute to the high efficacy observed in this compound.

Implications and Future Directions

  • Decitabine represents a novel antiviral candidate that could improve management of EHV-4 infections in horses.
  • Further in vivo studies are needed to confirm its safety and efficacy within living animals, including dosage optimization.
  • This study encourages exploration of antiviral drugs that can modulate the host immune response, not just directly target viruses.
  • Results may also stimulate more comprehensive screening efforts to find additional antivirals against equine herpesviruses.
  • Potential therapeutic strategies could combine compounds to simultaneously target viral replication and enhance innate immunity.

Cite This Article

APA
Normand C, Thieulent CJ, Fortier C, Sutton G, Senamaud-Beaufort C, Jourdren L, Blugeon C, Vidalain PO, Pronost S, Hue ES. (2024). A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response. Viruses, 16(5), 746. https://doi.org/10.3390/v16050746

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 16
Issue: 5
PII: 746

Researcher Affiliations

Normand, Camille
  • LABÉO, 14280 Saint-Contest, France.
  • Normandie Université, UNICAEN BIOTARGEN, 14280 Saint-Contest, France.
Thieulent, Côme J
  • Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
  • Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Fortier, Christine
  • LABÉO, 14280 Saint-Contest, France.
  • Normandie Université, UNICAEN BIOTARGEN, 14280 Saint-Contest, France.
  • Normandie Université, UNICAEN, ImpedanCELL, 14280 Saint-Contest, France.
Sutton, Gabrielle
  • Cytokines and Adaptive Immunity Lab, Sainte-Justine University Hospital and Research Center, University of Montréal, Montreal, QC H3T 1C5, Canada.
  • Microbiology, Infectiology and Immunology Department, Faculty of Medicine, University of Montréal, Montreal, QC H3T 1C5, Canada.
Senamaud-Beaufort, Catherine
  • GenomiqueENS, Institut de Biologie de l'ENS (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France.
Jourdren, Laurent
  • GenomiqueENS, Institut de Biologie de l'ENS (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France.
Blugeon, Corinne
  • GenomiqueENS, Institut de Biologie de l'ENS (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France.
Vidalain, Pierre-Olivier
  • 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.
Pronost, Stéphane
  • LABÉO, 14280 Saint-Contest, France.
  • Normandie Université, UNICAEN BIOTARGEN, 14280 Saint-Contest, France.
  • Normandie Université, UNICAEN, ImpedanCELL, 14280 Saint-Contest, France.
Hue, Erika S
  • LABÉO, 14280 Saint-Contest, France.
  • Normandie Université, UNICAEN BIOTARGEN, 14280 Saint-Contest, France.
  • Normandie Université, UNICAEN, ImpedanCELL, 14280 Saint-Contest, France.

MeSH Terms

  • Animals
  • Antiviral Agents / pharmacology
  • Cell Line
  • Decitabine / pharmacology
  • Drug Evaluation, Preclinical
  • Fibroblasts / drug effects
  • Fibroblasts / virology
  • Herpesviridae Infections / drug therapy
  • Herpesviridae Infections / virology
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / immunology
  • Herpesvirus 4, Equid / drug effects
  • Horse Diseases / virology
  • Horse Diseases / drug therapy
  • Horse Diseases / immunology
  • Horses
  • Immunity, Innate / drug effects
  • Viral Load / drug effects
  • Virus Replication / drug effects

Grant Funding

  • CS-2020-2023-023-HVE4_IRCP / IFCE (Institut Français du Cheval et de l'Equitation)
  • N49-2019 / Fonds Eperon

Conflict of Interest Statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Citations

This article has been cited 2 times.
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