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. 1995 Nov;69(11):7282–7285. doi: 10.1128/jvi.69.11.7282-7285.1995

Activation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite Leishmania donovani.

R Bernier 1, S J Turco 1, M Olivier 1, M Tremblay 1
PMCID: PMC189654  PMID: 7474154

Abstract

In this study, we demonstrated that the protozoan parasite Leishmania donovani and one of its major surface molecules, the lipophosphoglycan (LPG), can induce human immunodeficiency virus type 1 (HIV-1) expression in U1 and OM-10.1, two cell lines of monocytoid origin latently infected with HIV-1. Treatment of U1 cells with various concentrations of LPG (1, 5, and 10 microM) resulted in a dose-dependent secretion of tumor necrosis factor alpha (TNF-alpha). Suppression of LPG-induced HIV-1 expression by polyclonal anti-TNF-alpha antibodies further confirmed the involvement of this cytokine. Results from these studies indicate that the protozoan parasite L. donovani can induce the secretion of TNF-alpha that will function in an autocrine or paracrine manner to upregulate HIV-1 expression. Our data suggest for the first time that this protozoan parasite can be viewed as a potential cofactor in the pathogenesis of AIDS.

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Selected References

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  1. Alvar J. Leishmaniasis and AIDS co-infection: the Spanish example. Parasitol Today. 1994 Apr;10(4):160–163. doi: 10.1016/0169-4758(94)90270-4. [DOI] [PubMed] [Google Scholar]
  2. Alvar J., Verdejo J., Osuna A., Nájera R. Visceral leishmaniasis in a patient seropositive for HIV. Eur J Clin Microbiol. 1987 Oct;6(5):604–606. doi: 10.1007/BF02014266. [DOI] [PubMed] [Google Scholar]
  3. Ashford R. W., Desjeux P., Deraadt P. Estimation of population at risk of infection and number of cases of Leishmaniasis. Parasitol Today. 1992 Mar;8(3):104–105. doi: 10.1016/0169-4758(92)90249-2. [DOI] [PubMed] [Google Scholar]
  4. Butera S. T., Perez V. L., Wu B. Y., Nabel G. J., Folks T. M. Oscillation of the human immunodeficiency virus surface receptor is regulated by the state of viral activation in a CD4+ cell model of chronic infection. J Virol. 1991 Sep;65(9):4645–4653. doi: 10.1128/jvi.65.9.4645-4653.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Descoteaux A., Turco S. J., Sacks D. L., Matlashewski G. Leishmania donovani lipophosphoglycan selectively inhibits signal transduction in macrophages. J Immunol. 1991 Apr 15;146(8):2747–2753. [PubMed] [Google Scholar]
  6. Duh E. J., Maury W. J., Folks T. M., Fauci A. S., Rabson A. B. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974–5978. doi: 10.1073/pnas.86.15.5974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fauci A. S. Cytokine regulation of HIV expression. Lymphokine Res. 1990 Winter;9(4):527–531. [PubMed] [Google Scholar]
  8. Fernández-Guerrero M. L., Aguado J. M., Buzón L., Barros C., Montalbán C., Martín T., Bouza E. Visceral leishmaniasis in immunocompromised hosts. Am J Med. 1987 Dec;83(6):1098–1102. doi: 10.1016/0002-9343(87)90948-x. [DOI] [PubMed] [Google Scholar]
  9. Fillola G., Corberand J. X., Laharrague P. F., Levenes H., Massip P., Recco P. Peripheral intramonocytic leishmanias in an AIDS patient. J Clin Microbiol. 1992 Dec;30(12):3284–3285. doi: 10.1128/jcm.30.12.3284-3285.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Folks T. M., Clouse K. A., Justement J., Rabson A., Duh E., Kehrl J. H., Fauci A. S. Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2365–2368. doi: 10.1073/pnas.86.7.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Folks T. M., Justement J., Kinter A., Dinarello C. A., Fauci A. S. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science. 1987 Nov 6;238(4828):800–802. doi: 10.1126/science.3313729. [DOI] [PubMed] [Google Scholar]
  12. Gendelman H. E., Orenstein J. M., Baca L. M., Weiser B., Burger H., Kalter D. C., Meltzer M. S. The macrophage in the persistence and pathogenesis of HIV infection. AIDS. 1989 Aug;3(8):475–495. doi: 10.1097/00002030-198908000-00001. [DOI] [PubMed] [Google Scholar]
  13. Jeannel D., Tuppin P., Brucker G., Danis M., Gentilini M. Leishmaniasis in France. Lancet. 1989 Sep 30;2(8666):804–804. doi: 10.1016/s0140-6736(89)90868-4. [DOI] [PubMed] [Google Scholar]
  14. Margolick J. B., Volkman D. J., Folks T. M., Fauci A. S. Amplification of HTLV-III/LAV infection by antigen-induced activation of T cells and direct suppression by virus of lymphocyte blastogenic responses. J Immunol. 1987 Mar 15;138(6):1719–1723. [PubMed] [Google Scholar]
  15. Matsuyama T., Hamamoto Y., Soma G., Mizuno D., Yamamoto N., Kobayashi N. Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV): enhancement of HIV replication. J Virol. 1989 Jun;63(6):2504–2509. doi: 10.1128/jvi.63.6.2504-2509.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mellors J. W., Griffith B. P., Ortiz M. A., Landry M. L., Ryan J. L. Tumor necrosis factor-alpha/cachectin enhances human immunodeficiency virus type 1 replication in primary macrophages. J Infect Dis. 1991 Jan;163(1):78–82. doi: 10.1093/infdis/163.1.78. [DOI] [PubMed] [Google Scholar]
  17. Meltzer M. S., Skillman D. R., Gomatos P. J., Kalter D. C., Gendelman H. E. Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol. 1990;8:169–194. doi: 10.1146/annurev.iy.08.040190.001125. [DOI] [PubMed] [Google Scholar]
  18. Okamoto T., Ogiwara H., Hayashi T., Mitsui A., Kawabe T., Yodoi J. Human thioredoxin/adult T cell leukemia-derived factor activates the enhancer binding protein of human immunodeficiency virus type 1 by thiol redox control mechanism. Int Immunol. 1992 Jul;4(7):811–819. doi: 10.1093/intimm/4.7.811. [DOI] [PubMed] [Google Scholar]
  19. Orlandi P. A., Jr, Turco S. J. Structure of the lipid moiety of the Leishmania donovani lipophosphoglycan. J Biol Chem. 1987 Jul 25;262(21):10384–10391. [PubMed] [Google Scholar]
  20. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pisa P., Gennene M., Söder O., Ottenhoff T., Hansson M., Kiessling R. Serum tumor necrosis factor levels and disease dissemination in leprosy and leishmaniasis. J Infect Dis. 1990 May;161(5):988–991. doi: 10.1093/infdis/161.5.988. [DOI] [PubMed] [Google Scholar]
  22. Poli G., Bressler P., Kinter A., Duh E., Timmer W. C., Rabson A., Justement J. S., Stanley S., Fauci A. S. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med. 1990 Jul 1;172(1):151–158. doi: 10.1084/jem.172.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Poli G., Kinter A., Justement J. S., Kehrl J. H., Bressler P., Stanley S., Fauci A. S. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A. 1990 Jan;87(2):782–785. doi: 10.1073/pnas.87.2.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Turco S. J., Descoteaux A. The lipophosphoglycan of Leishmania parasites. Annu Rev Microbiol. 1992;46:65–94. doi: 10.1146/annurev.mi.46.100192.000433. [DOI] [PubMed] [Google Scholar]
  25. Turco S. J., Wilkerson M. A., Clawson D. R. Expression of an unusual acidic glycoconjugate in Leishmania donovani. J Biol Chem. 1984 Mar 25;259(6):3883–3889. [PubMed] [Google Scholar]
  26. Vyakarnam A., McKeating J., Meager A., Beverley P. C. Tumour necrosis factors (alpha, beta) induced by HIV-1 in peripheral blood mononuclear cells potentiate virus replication. AIDS. 1990 Jan;4(1):21–27. doi: 10.1097/00002030-199001000-00003. [DOI] [PubMed] [Google Scholar]

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