Destruction of primary CD4 T cells by cell–cell interaction in human immunodeficiency virus type 1 infection Free

Abstract

Infection of CD4 T lymphocytes with human immunodeficiency virus (HIV) is accompanied by extensive cytopathicity. The mechanism of cell death is unclear, but may be related to expression of the viral envelope glycoprotein. Here, it is demonstrated that T cell destruction in primary T cells occurs upon contact of infected with uninfected lymphocytes. Cell death was due to the interaction of the envelope glycoprotein with CD4 and subsequent fusion of the cells. Agents that interfered with cell-to-cell fusion such as a monoclonal antibody to CD4 and the peptide T20 prevented T cell death and depletion. In contrast, single-cell lysis due to expression and intracellular processing of the envelope glycoprotein was insignificant. These results suggest that cell-to-cell fusion and concomitant rapid cell death promote the depletion of T cells in HIV-infected individuals.

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2000-08-01
2024-03-29
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References

  1. Cao J., Park I.-W., Cooper A., Sodroski J. 1996; Molecular determinants of acute single-cell lysis by human immunodeficiency virus type 1. Journal of Virology 70:1340–1354
    [Google Scholar]
  2. Chesebro B., Wehrly K. 1988; Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity. Journal of Virology 62:3779–3788
    [Google Scholar]
  3. Corbeil J., Richman D. D. 1995; Productive infection and subsequent interaction of CD4–gp120 at the cellular membrane is required for HIV-induced apoptosis of CD4+ T cells. Journal of General Virology 76:681–690
    [Google Scholar]
  4. Frankel S. S., Wenig B. M., Burke A. P., Mannan P., Thompson L. D., Abbondanzo S. L., Nelson A. M., Pope M., Steinman R. M. 1996; Replication of HIV-1 in dendritic cell-derived syncytia at the mucosal surface of the adenoid. Science 272:115–117
    [Google Scholar]
  5. Heinkelein M., Sopper S., Jassoy C. 1995; Contact of human immunodeficiency virus type 1-infected and uninfected CD4+ T lymphocytes is highly cytolytic for both cells. /title>Journal of Virology 69:6925–6931
    [Google Scholar]
  6. Heinkelein M., Müller M., Kutsch O., Sopper S., Jassoy C. 1997; Rapid and selective depletion of CD4+ T lymphocytes and preferential loss of memory cells on interaction of mononuclear cells with HIV-1 glycoprotein-expressing cells. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 16:74–82
    [Google Scholar]
  7. Kilby J. M., Hopkins S., Venetta T. M., DiMassimo B., Cloud G. A., Lee J. Y., Alldredge L., Hunter E., Lambert D., Bolognesi D., Matthews T., Johnson M. R., Nowak M. A., Shaw G. M., Saag M. S. 1998; Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nature Medicine 4:1302–1307
    [Google Scholar]
  8. Koga Y., Sasaki M., Yoshida H., Wigzell H., Kimura G., Nomoto K. 1990; Cytopathic effect determined by the amount of CD4 molecules in human cell lines expressing envelope glycoprotein of HIV. Journal of Immunology 144:94–102
    [Google Scholar]
  9. Laurent-Crawford A. G., Krust B., Muller S., Rivière Y., Rey-Cuillé M.-A., Béchet J.-M., Montagnier L., Hovanessian A. G. 1991; The cytopathic effect of HIV is associated with apoptosis. Virology 185:829–839
    [Google Scholar]
  10. Laurent-Crawford A. G., Krust B., Rivière Y., Desgranges C., Muller S., Kieny M. P., Dauguet C., Hovanessian A. G. 1993; Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells. AIDS Research and Human Retroviruses 9:761–773
    [Google Scholar]
  11. Laurent-Crawford A. G., Coccia E., Krust B., Hovanessian A. G. 1995; Membrane-expressed HIV envelope glycoprotein heterodimer is a powerful inducer of cell death in uninfected CD4+ target cells. Research in Virology 146:5–17
    [Google Scholar]
  12. Leonard R., Zagury D., Desportes I., Bernard J., Zagury J.-F., Gallo R. C. 1988; Cytopathic effect of human immunodeficiency virus in T4 cells is linked to the last stages of virus infection. Proceedings of the National Academy of Sciences, USA 85:3570–3574
    [Google Scholar]
  13. Lifson J. D., Feinberg M. B., Reyes G. R., Rabin L., Banapour B., Chakrabarti S., Moss B., Wong-Staal F., Steimer K. S., Engleman E. G. 1986a; Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature 323:725–728
    [Google Scholar]
  14. Lifson J. D., Reyes G. R., McGrath M. S., Stein B. S., Engleman E. G. 1986b; AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science 232:1123–1127
    [Google Scholar]
  15. McCallus D. E., Ugen K. E., Sato A. I., Williams W. V., Weiner D. B. 1992; Construction of a recombinant bacterial human CD4 expression system producing a bioactive CD4 molecule. Viral Immunology 5:163–172
    [Google Scholar]
  16. Mellors J. W., Rinaldo C. R. Jr, Gupta P., White R. M., Todd J. A., Kingsley L. A. 1996; Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272:1167–1170
    [Google Scholar]
  17. Nardelli B., Gonzales C. J., Schechter M., Valentine F. T. 1995; CD4+ blood lymphocytes are rapidly killed in vitro by contact with autologous human immunodeficiency virus-infected cells. Proceedings of the National Academy of Sciences, USA 92:7312–7316
    [Google Scholar]
  18. Navia B. A., Cho E.-S., Petito C. K., Price R. W. 1986; The AIDS dementia complex: II. Neuropathology. Annals of Neurology 19:525–535
    [Google Scholar]
  19. Ohnimus H., Heinkelein M., Jassoy C. 1997; Apoptotic cell death upon contact of CD4+ T lymphocytes with HIV glycoprotein-expressing cells is mediated by caspases but bypasses CD95 (Fas/Apo-1) and TNF receptor 1. Journal of Immunology 159:5246–5252
    [Google Scholar]
  20. Pantaleo G. 1999; Unraveling the strands of HIV’s web. Nature Medicine 5:27–28
    [Google Scholar]
  21. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. 1986; Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 322:470–474
    [Google Scholar]
  22. Somasundaran M., Robinson H. L. 1987; A major mechanism of human immunodeficiency virus-induced cell killing does not involve cell fusion. Journal of Virology 61:3114–3119
    [Google Scholar]
  23. Wild C. T., Shugars D. C., Greenwell T. K., McDanal C. B., Matthews T. J. 1994; Peptides corresponding to a predictive α-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proceedings of the National Academy of Sciences, USA 91:9770–9774
    [Google Scholar]
  24. Yang O. O., Kalams S. A., Rosenzweig M., Trocha A., Jones N., Koziel M., Walker B. D., Johnson R. P. 1996; Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes. Journal of Virology 70:5799–5806
    [Google Scholar]
  25. Yoffe B., Lewis D. E., Petrie B. L., Noonan C. A., Melnick J. L., Hollinger F. B. 1987; Fusion as a mediator of cytolysis in mixtures of uninfected CD4+ lymphocytes and cells infected by human immunodeficiency virus. Proceedings of the National Academy of Sciences, USA 84:1429–1433
    [Google Scholar]
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