1887

Abstract

Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti-HIV drugs, the similarities in mechanism of replication suggest that some anti-HIV-1 drugs may also inhibit FeLV. This study demonstrates the anti-FeLV activity of four drugs approved by the US FDA (Food and Drug Administration) at non-toxic concentrations. Of these, tenofovir and raltegravir are anti-HIV-1 drugs, while decitabine and gemcitabine are approved to treat myelodysplastic syndromes and pancreatic cancer, respectively, but also have anti-HIV-1 activity in cell culture. Our results indicate that these drugs may be useful for FeLV treatment and should be investigated for mechanism of action and suitability for veterinary use.

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2012-04-01
2024-03-28
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References

  1. Bebenek K., Roberts J. D., Kunkel T. A. 1992; The effects of dNTP pool imbalances on frameshift fidelity during DNA replication. J Biol Chem 267:3589–3596[PubMed]
    [Google Scholar]
  2. Beck-Engeser G. B., Eilat D., Harrer T., Jäck H. M., Wabl M. 2009; Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir. Proc Natl Acad Sci U S A 106:20865–20870 [View Article][PubMed]
    [Google Scholar]
  3. Boyer P. L., Gao H. Q., Clark P. K., Sarafianos S. G., Arnold E., Hughes S. H. 2001; YADD mutants of human immunodeficiency virus type 1 and Moloney murine leukemia virus reverse transcriptase are resistant to lamivudine triphosphate (3TCTP) in vitro. J Virol 75:6321–6328 [View Article][PubMed]
    [Google Scholar]
  4. Buzón M. J., Massanella M., Llibre J. M., Esteve A., Dahl V., Puertas M. C., Gatell J. M., Domingo P., Paredes R.other authors 2010; HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 16:460–465 [View Article][PubMed]
    [Google Scholar]
  5. Cattori V., Tandon R., Riond B., Pepin A. C., Lutz H., Hofmann-Lehmann R. 2009; The kinetics of feline leukaemia virus shedding in experimentally infected cats are associated with infection outcome. Vet Microbiol 133:292–296 [View Article][PubMed]
    [Google Scholar]
  6. Cattori V., Weibel B., Lutz H. 2011; Inhibition of feline leukemia virus replication by the integrase inhibitor raltegravir. Vet Microbiol 152:165–168 [View Article][PubMed]
    [Google Scholar]
  7. Cerqueira N. M., Fernandes P. A., Ramos M. J. 2007; Understanding ribonucleotide reductase inactivation by gemcitabine. Chemistry 13:8507–8515 [View Article][PubMed]
    [Google Scholar]
  8. Clouser C. L., Patterson S. E., Mansky L. M. 2010; Exploiting drug repositioning for discovery of a novel HIV combination therapy. J Virol 84:9301–9309 [View Article][PubMed]
    [Google Scholar]
  9. Clouser C. L., Holtz C. M., Mullett M., Crankshaw D. L., Briggs J. E., Chauhan J., VanHoutan I. M., Patterson S. E., Mansky L. M. 2011; Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine. PLoS One 6:e15840 [View Article][PubMed]
    [Google Scholar]
  10. Essex M., Klein G., Snyder S. P., Harrold J. B. 1971; Correlation between humoral antibody and regression of tumours induced by feline sarcoma virus. Nature 233:195–196 [View Article][PubMed]
    [Google Scholar]
  11. Garcia J. S., Jain N., Godley L. A. 2010; An update on the safety and efficacy of decitabine in the treatment of myelodysplastic syndromes. Onco Targets Ther 3:1–13[PubMed]
    [Google Scholar]
  12. Gingerich D. A. 2008; Lymphocyte T-cell immunomodulator (LTCI): review of the immunopharmacology of a new veterinary biologic. Intern J Appl Res Vet Med 6:61–68
    [Google Scholar]
  13. Hartmann K., Block A., Ferk G., Vollmar A., Goldberg M., Lutz H. 1998; Treatment of feline leukemia virus-infected cats with paramunity inducer. Vet Immunol Immunopathol 65:267–275 [View Article][PubMed]
    [Google Scholar]
  14. Haschek W. M., Weigel R. M., Scherba G., DeVera M. C., Feinmehl R., Solter P., Tompkins M. B., Tompkins W. A. 1990; Zidovudine toxicity to cats infected with feline leukemia virus. Fundam Appl Toxicol 14:764–775 [View Article][PubMed]
    [Google Scholar]
  15. Jamburuthugoda V. K., Santos-Velazquez J. M., Skasko M., Operario D. J., Purohit V., Chugh P., Szymanski E. A., Wedekind J. E., Bambara R. A., Kim B. 2008; Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. J Biol Chem 283:9206–9216 [View Article][PubMed]
    [Google Scholar]
  16. Kearney B. P., Flaherty J. F., Shah J. 2004; Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. Clin Pharmacokinet 43:595–612 [View Article][PubMed]
    [Google Scholar]
  17. Malet I., Delelis O., Valantin M. A., Montes B., Soulie C., Wirden M., Tchertanov L., Peytavin G., Reynes J.other authors 2008; Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother 52:1351–1358 [View Article][PubMed]
    [Google Scholar]
  18. Operario D. J., Reynolds H. M., Kim B. 2005; Comparison of DNA polymerase activities between recombinant feline immunodeficiency and leukemia virus reverse transcriptases. Virology 335:106–121 [View Article][PubMed]
    [Google Scholar]
  19. Paprotka T., Venkatachari N. J., Chaipan C., Burdick R., Delviks-Frankenberry K. A., Hu W. S., Pathak V. K. 2010; Inhibition of xenotropic murine leukemia virus-related virus by APOBEC3 proteins and antiviral drugs. J Virol 84:5719–5729 [View Article][PubMed]
    [Google Scholar]
  20. Poch O., Sauvaget I., Delarue M., Tordo N. 1989; Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. EMBO J 8:3867–3874[PubMed]
    [Google Scholar]
  21. Reigadas S., Andréola M. L., Wittkop L., Cosnefroy O., Anies G., Recordon-Pinson P., Thiébaut R., Masquelier B., Fleury H. 2010; Evolution of 2-long terminal repeat (2-LTR) episomal HIV-1 DNA in raltegravir-treated patients and in in vitro infected cells. J Antimicrob Chemother 65:434–437 [View Article][PubMed]
    [Google Scholar]
  22. Rickard C. G., Post J. E., Noronha F., Barr L. M. 1969; A transmissible virus-induced lymphocytic leukemia of the cat. J Natl Cancer Inst 42:987–1014[PubMed]
    [Google Scholar]
  23. Robbins B. L., Srinivas R. V., Kim C., Bischofberger N., Fridland A. 1998; Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R-(2-phosphonomethoxypropyl)adenine (PMPA), bis(isopropyloxymethylcarbonyl)PMPA. Antimicrob Agents Chemother 42:612–617[PubMed]
    [Google Scholar]
  24. Rogerson P., Jarrett W., Mackey L. 1975; Epidemiological studies on feline leukaemia virus infection. I. A serological survey in urban cats. Int J Cancer 15:781–785 [View Article][PubMed]
    [Google Scholar]
  25. Singh I. R., Gorzynski J. E., Drobysheva D., Bassit L., Schinazi R. F. 2010; Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome. PLoS One 5:e9948 [View Article][PubMed]
    [Google Scholar]
  26. Smith R. A., Gottlieb G. S., Miller A. D. 2010; Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors. Retrovirology 7:70 [View Article][PubMed]
    [Google Scholar]
  27. Tavares L., Roneker C., Johnston K., Lehrman S. N., de Noronha F. 1987; 3′-Azido-3′-deoxythymidine in feline leukemia virus-infected cats: a model for therapy and prophylaxis of AIDS. Cancer Res 47:3190–3194[PubMed]
    [Google Scholar]
  28. Wang J., Lohman G. J., Stubbe J. 2009; Mechanism of inactivation of human ribonucleotide reductase with p53R2 by gemcitabine 5′-diphosphate. Biochemistry 48:11612–11621 [View Article][PubMed]
    [Google Scholar]
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