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Virus research2024; 350; 199503; doi: 10.1016/j.virusres.2024.199503

Efficacy assessment of antiretroviral drugs against equine infectious anemia virus in vitro.

Abstract: Equine infectious anemia virus (EIAV) is an equine lentivirus related to human immunodeficiency virus type 1 (HIV-1). Both viruses are related among the Retroviridae family, but their clinical manifestations are different as EIAV causes a long persistent infection with no progressive immune dysfunction in most cases. Today, no treatment is approved against EIAV, contrary to HIV-1, manageable through antiretroviral therapy, known as HAART (highly active antiretroviral therapy) or cART (combination antiretroviral therapy). No information about the efficacy of antiretroviral drugs against EIAV is available in the literature. This study evaluates the in vitro antiviral effect of eighteen FDA-approved antiretroviral compounds from different drug families, in an equine cells in vitro infection model with EIAV reference strain. Equine dermal cells, as well as equine peripheral blood mononuclear cells were treated with non-cytotoxic drug concentrations and infected with EIAV. Relative virus release in culture supernatants was assessed through relative quantification of viral RNA via RTqPCR and viral DNA comprising proviral integration in the cell genome was assessed through qPCR of infected cells, both after nucleic acid extractions. Out of eighteen tested drugs, thirteen showed a significant antiviral effect against EIAV in vitro, an interesting discovery showing the similarities between HIV-1 and EIAV and opening a possibility to treat equine infectious anemia to avoid the disease spread.
Publication Date: 2024-12-11 PubMed ID: 39613191PubMed Central: PMC11699113DOI: 10.1016/j.virusres.2024.199503Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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Overview

  • This study investigates the effectiveness of existing FDA-approved antiretroviral drugs, originally developed for HIV-1, against equine infectious anemia virus (EIAV) in laboratory cell cultures.
  • The researchers aim to determine which drugs can inhibit EIAV replication, which may lead to potential treatments for equine infectious anemia.

Introduction

  • Equine infectious anemia virus (EIAV) is a lentivirus, related to human immunodeficiency virus type 1 (HIV-1), both belonging to the Retroviridae family.
  • While HIV-1 causes progressive immune dysfunction in humans, EIAV typically causes a long-lasting infection in horses without severe immune system failure.
  • Currently, there is no approved treatment for EIAV, unlike HIV-1, which is managed with highly active antiretroviral therapy (HAART) or combination antiretroviral therapy (cART).
  • The effectiveness of antiretroviral drugs against EIAV has not previously been documented.

Research Objective

  • To evaluate the antiviral activity of 18 FDA-approved antiretroviral drugs against EIAV in vitro.
  • These drugs belong to different pharmacological families targeting various stages of the HIV-1 life cycle.
  • The study uses equine-derived cells to model EIAV infection and drug effects, making the findings relevant for potential real-world applications in horses.

Methods

  • Cell Models:
    • Equine dermal cells and equine peripheral blood mononuclear cells (PBMCs) were used, providing relevant host environments for EIAV replication.
  • Drug Treatment:
    • Cells were treated with non-cytotoxic concentrations of each antiretroviral drug to ensure that observed antiviral effects are not due to cell toxicity.
  • Infection and Assessment:
    • Following drug treatment, cells were infected with a reference strain of EIAV.
    • Relative virus release into the culture supernatant was measured by quantifying viral RNA via reverse transcription quantitative PCR (RT-qPCR).
    • Proviral DNA, indicating integrated virus within the host genome, was quantified by qPCR of infected cells.

Results

  • Out of 18 tested drugs, 13 demonstrated significant antiviral activity against EIAV in vitro.
  • This suggests a notable similarity in drug susceptibility between HIV-1 and EIAV despite their clinical differences.
  • The findings indicate that some existing HIV-1 antiretroviral drugs could be repurposed to inhibit EIAV replication.

Significance and Implications

  • The study is the first to document the antiviral activity of FDA-approved antiretroviral drugs against EIAV, providing crucial baseline data.
  • Successful inhibition of EIAV in vitro opens the possibility for developing treatment options for equine infectious anemia, a disease currently lacking approved therapies.
  • Treatment could potentially reduce viral spread among horse populations and help control the disease burden.
  • Further in vivo studies are necessary to confirm safety and efficacy of these drugs in horses.

Conclusions

  • This research identifies that multiple antiretroviral drugs targeting HIV-1 can also significantly inhibit EIAV replication in cell culture.
  • The study provides a foundation for exploring antiviral treatments for EIAV, which could change the management of equine infectious anemia.
  • Future work should focus on clinical trials and dosing studies to translate these findings into practical veterinary therapies.

Cite This Article

APA
(2024). Efficacy assessment of antiretroviral drugs against equine infectious anemia virus in vitro. Virus Res, 350, 199503. https://doi.org/10.1016/j.virusres.2024.199503

Publication

ISSN: 1872-7492
NlmUniqueID: 8410979
Country: Netherlands
Language: English
Volume: 350
Pages: 199503
PII: 199503

Researcher Affiliations

MeSH Terms

  • Infectious Anemia Virus, Equine / drug effects
  • Infectious Anemia Virus, Equine / genetics
  • Animals
  • Horses
  • Leukocytes, Mononuclear / virology
  • Leukocytes, Mononuclear / drug effects
  • Equine Infectious Anemia / virology
  • Equine Infectious Anemia / drug therapy
  • Anti-Retroviral Agents / pharmacology
  • RNA, Viral / genetics
  • Antiviral Agents / pharmacology
  • Virus Replication / drug effects
  • Cells, Cultured
  • DNA, Viral / genetics

Conflict of Interest Statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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