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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.
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
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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

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 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

Virus research
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.

References

This article includes 38 references
  1. Auwerx J, North TW, Preston BD, Klarmann GJ, De Clercq E, Balzarini J. Chimeric human immunodeficiency virus type 1 and feline immunodeficiency virus reverse transcriptases: role of the subunits in resistance/sensitivity to non-nucleoside reverse transcriptase inhibitors.. Mol. Pharmacol. 2002;61(2):400–406.
    doi: 10.1124/mol.61.2.400pubmed: 11809865google scholar: lookup
  2. Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C. Isolation of a T-Lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220(4599):868–871.
    doi: 10.1126/science.6189183pubmed: 6189183google scholar: lookup
  3. Bisset LR, Lutz H, Böni J, Hofmann-Lehmann R, Lüthy R, Schüpbach J. Combined effect of zidovudine (ZDV), lamivudine (3TC) and abacavir (ABC) antiretroviral therapy in suppressing in vitro FIV replication.. Antiviral Res. 2002;53(1):35–45.
    doi: 10.1016/S0166-3542(01)00190-5pubmed: 11684314google scholar: lookup
  4. Borman AM, Paulous S, Clavel F. Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug.. J. General Virol. 1996;77(3):419–426.
    doi: 10.1099/0022-1317-77-3-419pubmed: 8601776google scholar: lookup
  5. Clapham PR, McKnight Á. Cell surface receptors, virus entry and tropism of primate lentiviruses.. J. Gener. Virol. 2002;83(8):1809–1829.
    doi: 10.1099/0022-1317-83-8-1809pubmed: 12124446google scholar: lookup
  6. De Parseval A, Chatterji U, Sun P, Elder JH. Feline immunodeficiency virus targets activated CD4 T cells by using CD134 as a binding receptor.. Proceed. Nation. Acad. Sci. 2004;101(35):13044–13049.
    doi: 10.1073/pnas.0404006101pmc: PMC516514pubmed: 15326292google scholar: lookup
  7. Deeks ED. Bictegravir/emtricitabine/tenofovir alafenamide: a review in HIV-1 infection.. Drugs 2018;78(17):1817–1828.
    doi: 10.1007/s40265-018-1010-7pmc: PMC6424950pubmed: 30460547google scholar: lookup
  8. Di Perri G. Pharmacological outlook of lenacapavir: a novel first-in-class long-acting HIV-1 capsid inhibitor.. Infezioni in Medicina 2023;31(4).
    doi: 10.53854/liim-3104-8pmc: PMC10705863pubmed: 38075416google scholar: lookup
  9. Elder JH, Sundstrom M, Rozieres SD, Parseval AD, Grant CK, Lin Y-C. Molecular mechanisms of FIV infection.. Vet. Immunol. Immunopathol. 2008;123(1–2):3–13.
    doi: 10.1016/j.vetimm.2008.01.007pmc: PMC2409060pubmed: 18289701google scholar: lookup
  10. Engelman AN. Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition.. J. Biolog. Chem. 2019;294(41):15137–15157.
    doi: 10.1074/jbc.REV119.006901pmc: PMC6791320pubmed: 31467082google scholar: lookup
  11. Fanales-Belasio E, Raimondo M, Suligoi B, Buttò S. HIV virology and pathogenetic mechanisms of infection: a brief overview.. Annali Dell'Istituto Superiore Di Sanita 2010;46(1):5–14.
    doi: 10.4415/ANN_10_01_02pubmed: 20348614google scholar: lookup
  12. Gaudaire D, Merlin A, Tapprest J, Delerue M, Grandcollot-Chabot M, HANS A. Deux nouveaux foyers d'anémie infectieuse des equidés en dordogne et en haute-savoie déclarés à l'automne 2019. 2019.
  13. Hart S, Nolte I. Long-term treatment of diseased, FIV-seropositive field cats with azidothymidine (AZT). J. Veterin. Med. Series A 1995;42(1–10):397–409.
    doi: 10.1111/j.1439-0442.1995.tb00392.xpubmed: 7495172google scholar: lookup
  14. Hartmann K, Wooding A, Bergmann M. Efficacy of antiviral drugs against feline immunodeficiency virus.. Vet. Sci. 2015;2(4):456–476.
    doi: 10.3390/vetsci2040456pmc: PMC5644647pubmed: 29061953google scholar: lookup
  15. Hawkins JA, Adams WV, Wilson BH, Issel CJ, Roth EE. Transmission of equine infectious anemia virus by Tabanus Fuscicostatus.. J. Am. Vet. Med. Assoc. 1976;168(1):63–64.
    pubmed: 942712
  16. Holec AD, Mandal S, Prathipati PK, Destache CJ. Nucleotide reverse transcriptase inhibitors: a thorough review, present status and future perspective as HIV therapeutics.. Curr. HIV Res. 2017;15(6):411–421.
    doi: 10.2174/1570162X15666171120110145pmc: PMC7219633pubmed: 29165087google scholar: lookup
  17. Issel CJ, Cook RF, Mealey RH, Horohov DW. Equine infectious anemia in 2014: live with it or eradicate it?. Veterin. Clinics North America 2014;30(3):561–577.
    doi: 10.1016/j.cveq.2014.08.002pubmed: 25441114google scholar: lookup
  18. Jin S, Chen C, Montelaro RC. Equine infectious anemia virus gag p9 function in early steps of virus infection and provirus production.. J. Virol. 2005;79(14):8793–8801.
    doi: 10.1128/JVI.79.14.8793-8801.2005pmc: PMC1168773pubmed: 15994773google scholar: lookup
  19. Kervinen J, Lubkowski J, Zdanov A, Bhatt D, Dunn BM, Hui KY, Powell DJ, Kay J, Wlodawer A, Gustchina A. Toward a universal inhibitor of retroviral proteases: comparative analysis of the interactions of LP-130 complexed with proteases from HIV-1, FIV, and EIAV’. Protein Sci. 1998;7(11):2314–2323.
    doi: 10.1002/pro.5560071108pmc: PMC2143868pubmed: 9827997google scholar: lookup
  20. Langtry HD, Campoli-Richards DM. Zidovudine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.. Drugs 1989;37(4):408–450.
    doi: 10.2165/00003495-198937040-00003pubmed: 2661194google scholar: lookup
  21. Larder BA, Darby G, Richman DD. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy.. Science (1979) 1989;243(4899):1731–1734.
    doi: 10.1126/science.2467383pubmed: 2467383google scholar: lookup
  22. Leroux C, Cadoré JL, Montelaro RC. Equine infectious anemia virus (EIAV): what has HIV's country cousin got to tell us?. Vet. Res. 2004;35(4):485–512.
    doi: 10.1051/vetres:2004020pubmed: 15236678google scholar: lookup
  23. Lin YZ, Shen RX, Zhu ZY, Deng XL, Cao XZ, Wang XF, Ma J. An attenuated EIAV vaccine strain induces significantly different immune responses from its pathogenic parental strain although with similar in vivo replication pattern.. Antiviral Res. 2011;92(2):292–304.
    doi: 10.1016/j.antiviral.2011.08.016pubmed: 21893100google scholar: lookup
  24. Namasivayam V, Vanangamudi M, Kramer VG, Kurup S, Zhan P, Liu X, Kongsted J, Byrareddy SN. The journey of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) from lab to clinic.. J. Med. Chem. 2019;62(10):4851–4883.
    doi: 10.1021/acs.jmedchem.8b00843pmc: PMC7049092pubmed: 30516990google scholar: lookup
  25. Norelli S, Daker S, D'Ostilio D, Mele F, Mancini F, Taglia F, Ruggieri A. Response of feline immunodeficiency virus (FIV) to tipranavir may provide new clues for development of broad-based inhibitors of retroviral proteases acting on drug-resistant HIV-1.. Curr. HIV Res. 2008;6(4):306–317.
    doi: 10.2174/157016208785132527pubmed: 18691029google scholar: lookup
  26. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection’. England J. Med. 1998;338(13):853–860.
    doi: 10.1056/NEJM199803263381301pubmed: 9516219google scholar: lookup
  27. Palmisano L, Vella S. A brief history of antiretroviral therapy of HIV infection: success and challenges.. Annali Dell'Istituto Superiore Di Sanita 2011;47(1):44–48.
    doi: 10.4415/ANN_11_01_10pubmed: 21430338google scholar: lookup
  28. Powell DJ, Bur D, Wlodawer A, Gustchina A, Payne SL, Dunn BM, Kay J. Expression, characterisation and mutagenesis of the aspartic proteinase from equine infectious anaemia virus.. Eur. J. Biochem. 1996;241(2):664–674.
    doi: 10.1111/j.1432-1033.1996.00664.xpubmed: 8917470google scholar: lookup
  29. Schnölzer M, Rackwitz HR, Gustchina A, Laco GS, Wlodawer A, Elder JH, Kent SBH. Comparative properties of feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) proteinases prepared by total chemical synthesis.. Virology 1996;224(1):268–275.
    doi: 10.1006/viro.1996.0528pubmed: 8862421google scholar: lookup
  30. Schwartz AM, McCrackin MA, Schinazi RF, Hill PB, Vahlenkamp TW, Tompkins MB, Hartmann K. Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells.. Am. J. Vet. Res. 2014;75(3):273–281.
    doi: 10.2460/ajvr.75.3.273pubmed: 24564313google scholar: lookup
  31. Shin Y, Hyun C, Park M, Yoon CH. An overview of human immunodeficiency virus-1 antiretroviral drugs: general principles and current status.. Infect. ChemOther. 2021;53(1):29.
    doi: 10.3947/ic.2020.0100pmc: PMC8032919pubmed: 34409780google scholar: lookup
  32. Smyth NR, McCracken C, Gaskell RM, Cameron JM, Coates JAV, Gaskell CJ, Hart CA, Bennett M. Susceptibility in cell culture of feline immunodeficiency virus to eighteen antiviral agents.. J. Antimicrob. Chemother. 1994;34(4):589–594.
    doi: 10.1093/jac/34.4.589pubmed: 7532645google scholar: lookup
  33. Togami H, Shimura K, Okamoto M, Yoshikawa R, Miyazawa T, Matsuoka M. Comprehensive in vitro analysis of simian retrovirus type 4 susceptibility to antiretroviral agents.. J. Virol. 2013;87(8):4322–4329.
    doi: 10.1128/JVI.03208-12pmc: PMC3624392pubmed: 23365453google scholar: lookup
  34. Vallée H, Carré H. Sur la nature infectieuse de l'anémie du cheval.. CR Acad. Sci. 1904;139:1239.
  35. Vanangamudi M, Palaniappan S, Kumaradoss KM, Namasivayam V. Strategies in the design and development of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Viruses 2023;15(10):1992.
    doi: 10.3390/v15101992pmc: PMC10610861pubmed: 37896769google scholar: lookup
  36. . ‘HIV – number of people (All ages) living with HIV, https://Www.Who.Int/Data/Gho/Data/Indicators/Indicator-Details/GHO/Estimated-Number-of-People–Living-with-Hiv, (Accessed Apr. 19 2024)’. .
  37. Wild CT, Shugars DC, Greenwell TK, McDanal CB, Matthews TJ. Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 Gp41 are potent inhibitors of virus infection.. Proceed. Nation. Acad. Sci. 1994;91(21):9770–9774.
    doi: 10.1073/pnas.91.21.9770pmc: PMC44898pubmed: 7937889google scholar: lookup
  38. Zhang B, Jin S, Jin J, Li F, Montelaro RC. A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus.. Proceed. Nation. Acad. Sci. 2005;102(28):9918–9923.
    doi: 10.1073/pnas.0501560102pmc: PMC1174982pubmed: 15985554google scholar: lookup

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