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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.039909-0
2012-04-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/4/900.html?itemId=/content/journal/jgv/10.1099/vir.0.039909-0&mimeType=html&fmt=ahah

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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][PubMed]
    [Google Scholar]
  7. Cerqueira N. M., Fernandes P. A., Ramos M. J.. ( 2007;). Understanding ribonucleotide reductase inactivation by gemcitabine. . Chemistry 13:, 8507–8515. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][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. [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.039909-0
Loading
/content/journal/jgv/10.1099/vir.0.039909-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error