1887

Abstract

Recombinant interleukin 4 (IL-4) stimulated extracellular (EC) and intracellular (IC) production of human immunodeficiency virus (HIV) from infected human blood-derived monocytes and macrophages when incubated with the cells after but not before virus inoculation. Significant stimulation was observed in 20 of 27 experiments with monocytes (inoculated with HIV immediately after adherence) and 10 of 13 experiments with macrophages (inoculated after 5 days adherence) using a total of 30 normal donors of monocytes and macrophages, and 11 recent isolates of monocytotropic HIV strains (after one passage in mononuclear cells). Marked increases in EC and IC HIV antigen were observed in some experiments, which were comparable with the maximal stimulatory effects of other cytokines such as IL-2. IL-4 also had similar effects on infectious HIV concentration as measured by reverse transcriptase and TCID assays. Antibody to IL-4 prevented the stimulatory effect of the cytokine. The proportion of monocytes and macrophages infected by HIV, as determined by hybridization, also increased after incubation with IL-4 for 7 days. The most marked effects were observed with HIV-infected macrophages, for which the proportion of unstimulated infected cells was lower (35 to 45% increasing to 66 to 70% with IL-4 treatment). There was also an increased proportion of cells with high granule concentrations, suggesting that IL-4 increases the intracellular concentration of viral nucleic acids. This was supported by semi-quantitative hybridization experiments showing that total HIV RNA increased in IL-4-stimulated monocytes 48 to 96 h after HIV inoculation. A marked increase in aggregates was observed on day 7 in HIV-infected monocytes treated with IL-4, compared to that in HIV-infected cells alone or IL-4-treated uninfected monocytes. These findings suggest that IL-4 stimulates HIV replication in the early phases of infection and may also facilitate virus transmission by aggregate formation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-4-941
1992-04-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/73/4/JV0730040941.html?itemId=/content/journal/jgv/10.1099/0022-1317-73-4-941&mimeType=html&fmt=ahah

References

  1. Bachelerie F., Alcami J., Arenzana-Seisdedos F., Virelizier J. L. 1991; HIV enhancer activity perpetuated by NFkB induction on infection of monocytes. Nature, London 350:709–713
    [Google Scholar]
  2. Cunningham A. L., Merigan T. C. 1984; Leu3 positive T lymphocytes produce gamma interferon in patients with recurrent herpes labialis. Journal of Immunology 132:197–202
    [Google Scholar]
  3. Elliott M. J., Gamble J. R., Park L. S., Vadas M. A., Lopez A. F. 1991; Inhibition of human monocyte adhesion by interleukin 4. Blood (in press)
    [Google Scholar]
  4. Folks T. M., Clouse K. A., Justement J., Rabson A., Duh E., Kehrl J. H., Fauci A. S. 1989; Tumour necrosis factor alpha induces expression of human immunodeficièncy virus in a chronically infected T-cell clone. Proceedings of the National Academy of Sciences, U.S.A 86:2365–2374
    [Google Scholar]
  5. Gartner S., Markovitis P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. 1986; The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219
    [Google Scholar]
  6. Gendelman H. E., Orentstein J. M., Martin M. A., Ferrura C., Mitra R., Phipps T., Wahl L. A., Clifford-Lane C. H., Fauci A. S., Burke D. S., Skilliman D., Meltzer M. S. 1988; Efficient isolation and propagation of human immunodeficiency virus in recombinant colony-stimulating factor 1-treated monocytes. Journal of Experimental Medicine 167:1428–1441
    [Google Scholar]
  7. Goudsmit J., Wolf F., Paul D. A., Epstein L. G., Lange J. M. A., Krone W. J. A., Speelman H., Wolters E. C., van der Noordaa J., van der Helm H. J., Oleske J. M., Coutinho R. A. 1986; Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection. Lancet ii:177–180
    [Google Scholar]
  8. Griffin G. E., Leung K., Folks T. M., Kundel S., Nabel G. J. 1989; Activation of HIV gene expression during monocyte differentiation by induction of NF-kB. Nature, London 339:70–73
    [Google Scholar]
  9. Hammer S. M., Gillis J. M., Groopman J. E., Rose R. M. 1986; In vitro modification of human immunodeficiency virus infection by granulocyte-macrophage colony stimulating factor and gamma interferon. Proceedings of the National Academy of Sciences, U.S.A 83:8734–8738
    [Google Scholar]
  10. Ho D. D., Rota T. R., Hirsch M. S. 1986; Infection of monocyte/macrophages by human T lymphotropic virus type III. Journal of Clinical Investigation 77:1712–1715
    [Google Scholar]
  11. Hoffman A. B., Banapour B., Levy J. A. 1985; Characterization of the AIDS associated retrovirus reverse transcriptase and optimal conditions for the detection of virions. Virology 147:326–335
    [Google Scholar]
  12. Justement J., Poli G., Kinter A. L., Bresser P., Kehrl J. H., Fauci A. S. 1991; Transforming growth factor beta (TGF-beta) exerts dichotomous effects on HIV expression in mononuclear phagocytes (MP). Abstract WA. 17 VIIth International Conference on AIDS, Florence, June 1991
    [Google Scholar]
  13. Kazazi F., Mathijs J.-M., Foley P., Cunningham A. L. 1989; Variations in CD4 expression by human monocytes and macrophages and their relationship to infection with the human immunodeficiency virus. Journal of General Virology 70:2661–2672
    [Google Scholar]
  14. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. 1986; Detection of AIDS virus in macrophages in brain tissues from AIDS patients with encephalopathy. Science 233:1089–1093
    [Google Scholar]
  15. Kornbluth R. S., Oh P. S., Munis J. R., Cleveland P. H., Richman D. D. 1989; Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro . Journal of Experimental Medicine 169:1137–1151
    [Google Scholar]
  16. Kornbluth R. S., Oh P. S., Munis J. R., Cleveland P. H., Richmond D. D. 1990; The role of interferons in the control of HIV replication in macrophages. Clinical Immunology and Immuno-pathology 54:200–219
    [Google Scholar]
  17. Koyangi Y., O’Brien W. A., Zhao J. Q., Golde D. W., Gasson J. C., Chen I. S. Y. 1988; Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Science 241:1673–1675
    [Google Scholar]
  18. Lauener R. P., Goyert S. M., Geha R. S., Vercelli D. 1990; Interleukin 4 down-regulates the expression of CD14 in normal human monocytes. European Journal of Immunology 20:2375–2381
    [Google Scholar]
  19. Lenardo M. J., Baltimore D. 1989; NF-kB: a pleiotropic mediator of inducible and tissue-specific gene control. Cell 58:227–229
    [Google Scholar]
  20. Lifson J. D., Reyes G. R., McGrath M. S., Stein B. S., Engleman E. G. 1986; AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science 232:1132–1137
    [Google Scholar]
  21. Littman B. H., Dastvan F. F., Carlson P. L., Sanders K. M. 1989; Regulation of monocyte/macrophages C3 production and HLA-DR expression by IL-4 (BSF-1) and IFN-gamma. Journal of Immunology 142:520–525
    [Google Scholar]
  22. McElrath M. J., Pruett J. E., Cohn Z. A. 1989; Mononuclear phagocytes of blood and bone marrow: comparative roles as viral reservoirs in human immunodeficiency virus type 1 infections. Proceedings of the National Academy of Sciences, U.S.A 86:675–682
    [Google Scholar]
  23. McInnes A., Rennick D. M. 1988; Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells. Journal of Experimental Medicine 167:598–611
    [Google Scholar]
  24. Matsuyama T., Yoshiyama H., Hamamoto Y., Yamamoto N., Soma G., Mizuno D., Kobayashi N. 1989; Enhancement of HIV replication and giant cell formation by tumour necrosis factor. AIDS Research and Human Retroviruses 5:139–146
    [Google Scholar]
  25. Molina J.-M., Schindler R., Ferriani R., Sakaguchi M., Vannier E., Dinarello C. A., Groopman J. E. 1990; Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1). Journal of Infectious Diseases 161:888–893
    [Google Scholar]
  26. Nakajima K., Martinez-Mazo O., Hirano T., Salazar-Gonzalez J. F., Fahey J. L., Breen E. C., Nishanian P. G., Kishimoto T. 1989; Induction of IL-6 production by HIV. Journal of Immunology 142:531–536
    [Google Scholar]
  27. Newell A. L., Malkovsky O., Orr D., Taylor-Robinson D., Dalgleish A. G. 1987; Antigen test versus reverse transcriptase assay for detecting HIV. Lancet ii:1146–1147
    [Google Scholar]
  28. Nicholson J. K. A., Cross G. D., Gallaway C. S., McDougall J. S. 1986; In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). Journal of Immunology 137:323–329
    [Google Scholar]
  29. Novak R. M., Holzer T. J., Kennedy M. M., Heynen C. A., Dawson G. 1990; The effect of interleukin 4 (BSF-1) on infection of peripheral blood monocyte-derived macrophages with HIV-1. AIDS Research and Human Retroviruses 6:973–977
    [Google Scholar]
  30. Osborn L., Kundel S., Nabel G. J. 1989; Tumour necrosis factor-alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor, kB. Proceedings of the National Academy of Sciences, U.S.A 86:23362340
    [Google Scholar]
  31. Parrott C., Seidner T., Duh E., Leonard J., Theodore T. S., Buckler-White A., Martin M. A., Rabson A. B. 1991; Variable role of the long terminal repeat Spl binding sites in human immunodeficiency replication in T lymphocytes. Journal of Virology 65:1414–1419
    [Google Scholar]
  32. Poli G. A., Kinter J. S., Justement J. H., Kehrl J. H., Bressler P., Stanley S., Fauci A. S. 1989; Tumour necrosis factor-alpha functions in an autocrine manner in the induction of HIV expression. Proceedings of the National Academy of Sciences, U.S.A 87:872–791
    [Google Scholar]
  33. Poli G., Bressler P., Kinter A., Duh E., Timmer W. C., Rabson A., Justement J. S., Stanley S., Fauci A. S. 1990; Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumour necrosis factor by transcriptional and post-transcriptional mechanisms. Journal of Experimental Medicine 172:151–158
    [Google Scholar]
  34. Poli G., Kinter A. L., Justement J. S., Bressler P., Kehrl J. H., Fauci A. S. 1991; Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in the infected cells of the monocyte/macrophage lineage. Journal of Experimental Medicine 173:509–597
    [Google Scholar]
  35. Potts B. J., Maury W., Martin M. A. 1990; Replication of HIV-1 in primary monocyte cultures. Journal of Virology 175:465–476
    [Google Scholar]
  36. Ryan J., Geczy C. L. 1988; Macrophage procoagulant-inducing factor: in vivo properties and chemotactic activity for phagocytic cells. Journal of Immunology 141:1819–1827
    [Google Scholar]
  37. Salahuddin S. Z., Rose R. M., Groopman J. E., Markham P. D., Gallo R. C. 1986; Human T lymphotropic virus type III infection of human alveolar macrophages. Blood 68:281–284
    [Google Scholar]
  38. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual 2nd edn New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  39. Valentin A., Matsuda S., Asjo B. 1990a; Characterization of the in vitro maturation of monocytes and the susceptibility to HIV infection. AIDS Research and Human Retroviruses 6:977–983
    [Google Scholar]
  40. Valentin A., Lundin K., Patarroyo M., Asjo B. 1990b; The leucocyte adhesion glycoprotein, CD18, particles in HIV-1 induced syncytia formation in monocytoid cells and T-cells. Journal of Immunology 144:934–937
    [Google Scholar]
  41. Wieser M., Bonnifer R., Oster W., Lindemann A., Mertelsmann R., Hermann I. 1989; Interleukin-4 induces secretion of CSF from granulocytes and CSF for macrophages by peripheral blood monocytes. Blood 73:1165–1168
    [Google Scholar]
  42. Yam L. T., Li C. Y., Crosby W. H. 1971; Cytochemical identification of monocytes and granulocytes. American Journal of Clinical Pathology 55:282–290
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-73-4-941
Loading
/content/journal/jgv/10.1099/0022-1317-73-4-941
Loading

Data & Media loading...

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