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Home / Equine Research Bank / Vet Res / An equine iPSC-based phenotypic screening platform identifie...
Veterinary research2024; 55(1); 32; doi: 10.1186/s13567-024-01290-1

An equine iPSC-based phenotypic screening platform identifies pro- and anti-viral molecules against West Nile virus.

Abstract: Outbreaks of West Nile virus (WNV) occur periodically, affecting both human and equine populations. There are no vaccines for humans, and those commercialised for horses do not have sufficient coverage. Specific antiviral treatments do not exist. Many drug discovery studies have been conducted, but since rodent or primate cell lines are normally used, results cannot always be transposed to horses. There is thus a need to develop relevant equine cellular models. Here, we used induced pluripotent stem cells to develop a new in vitro model of WNV-infected equine brain cells suitable for microplate assay, and assessed the cytotoxicity and antiviral activity of forty-one chemical compounds. We found that one nucleoside analog, 2'C-methylcytidine, blocked WNV infection in equine brain cells, whereas other compounds were either toxic or ineffective, despite some displaying anti-viral activity in human cell lines. We also revealed an unexpected proviral effect of statins in WNV-infected equine brain cells. Our results thus identify a potential lead for future drug development and underscore the importance of using a tissue- and species-relevant cellular model for assessing the activity of antiviral compounds.
© 2024. The Author(s).
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Publication Date: 2024-03-16 PubMed ID: 38493182PubMed Central: PMC10943879DOI: 10.1186/s13567-024-01290-1Google Scholar: Lookup
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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.

An in vitro model using equine induced pluripotent stem cell-derived brain cells was developed to screen chemicals for antiviral activity against West Nile virus (WNV), identifying a promising antiviral compound and revealing species-specific drug effects.

Background and Motivation

  • West Nile virus (WNV) causes outbreaks impacting humans and horses worldwide.
  • No vaccines are available for humans, and horse vaccines do not provide complete protection.
  • No specific antiviral treatments for WNV currently exist.
  • Previous drug discovery research largely used rodent or primate cell lines.
  • Results from these models may not translate well to equine biology or antiviral responses.
  • There is a critical need for relevant equine-specific cellular models to improve drug screening accuracy.

Research Objective

  • To develop a new in vitro model of equine brain cells infected with WNV using induced pluripotent stem cells (iPSCs).
  • To use this model for high-throughput phenotypic screening of antiviral chemical compounds.
  • To evaluate both cytotoxicity (cell safety) and antiviral efficacy of various compounds specifically in equine cells.

Methodology

  • Generated equine brain cells from induced pluripotent stem cells, providing a relevant cell type for WNV infection studies.
  • Set up microplate-based assay systems conducive to screening multiple compounds efficiently.
  • Screened a panel of 41 chemical compounds, including nucleoside analogs and other known antiviral agents.
  • Measured the effects on WNV infection rates in equine brain cells and assessed compound toxicity to cells.

Key Findings

  • Identified one nucleoside analog, 2’C-methylcytidine, which significantly inhibited WNV infection in equine brain cells.
  • Many tested compounds that showed anti-WNV activity in human cell lines were either ineffective or toxic in the equine model.
  • Unexpectedly found that statins, commonly used cholesterol-lowering drugs, had a proviral effect (enhancing virus infection) in equine brain cells, contrary to some previous assumptions or findings in other species.

Implications and Conclusions

  • The study provides a promising lead compound (2’C-methylcytidine) for future development of WNV antivirals suitable for horses.
  • It underscores the importance of using tissue- and species-relevant cellular models to obtain accurate efficacy and toxicity data for antiviral drug screening.
  • Species differences in drug response, such as the proviral effect of statins in equine cells, show that relying solely on non-equine models can be misleading for veterinary therapeutics.
  • This equine iPSC-based platform is a valuable tool to accelerate drug discovery for WNV and possibly other equine viral diseases.

Cite This Article

APA
Cochet M, Piumi F, Gorna K, Berry N, Gonzalez G, Danckaert A, Aulner N, Blanchet O, Zientara S, Donadeu FX, Munier-Lehmann H, Richardson J, Benchoua A, Coulpier M. (2024). An equine iPSC-based phenotypic screening platform identifies pro- and anti-viral molecules against West Nile virus. Vet Res, 55(1), 32. https://doi.org/10.1186/s13567-024-01290-1

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 55
Issue: 1
Pages: 32
PII: 32

Researcher Affiliations

Cochet, Marielle
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Piumi, François
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Gorna, Kamila
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Berry, Noémie
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Gonzalez, Gaëlle
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Danckaert, Anne
  • UTechS Photonics Bioimaging/C2RT, Institut Pasteur Paris, Université Paris Cité, 75015, Paris, France.
Aulner, Nathalie
  • UTechS Photonics Bioimaging/C2RT, Institut Pasteur Paris, Université Paris Cité, 75015, Paris, France.
Blanchet, Odile
  • Centre de Ressources Biologiques, BB-0033-00038, CHU Angers, 49933, Angers, France.
Zientara, Stéphan
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Donadeu, Francesc Xavier
  • Division of Translational Bioscience, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
Munier-Lehmann, Hélène
  • CNRS UMR3523, PF-CCB, Institut Pasteur, Université Paris Cité, 75015, Paris, France.
Richardson, Jennifer
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Benchoua, Alexandra
  • CECS, I-STEM, AFM, 91100, Evry, France.
Coulpier, Muriel
  • UMR VIROLOGIE, Laboratoire de Santé Animale, INRAE, Anses, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France. muriel.coulpier@vet-alfort.fr.

MeSH Terms

  • Animals
  • Horses
  • Humans
  • West Nile virus
  • Induced Pluripotent Stem Cells
  • West Nile Fever / veterinary
  • West Nile Fever / epidemiology
  • Brain
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Horse Diseases / drug therapy

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 2 times.
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