1887

Abstract

Most human immunodeficiency virus (HIV)-infected individuals show evidence of infection by only one strain of the virus despite possible frequent contact with multiple strains. The reason(s) for the emergence of a dominant strain of virus in HIV-infected people and the mechanism(s) which prevent other strains from establishing an infection is not known. In the present study, we demonstrate that peripheral blood mononuclear cells (PBMC) of asymptomatic HIV-infected individuals can resist productive infection by HIV-1 and HIV-2 strains. Although the PBMC of these individuals are resistant to superinfection, their CD4 cells are susceptible to infection. Moreover, two weeks after infection of their PBMC in culture, the superinfecting virus can be recovered from isolated CD4 cells. When CD8 cells from asymptomatic individuals are added to the superinfected CD4 cells, replication of the exogenously introduced virus is inhibited. In contrast, PBMC from individuals who have progressed to disease (Progressors) do not resist superinfection and their CD8 cells do not show the antiviral activity which controls productive HIV infection. These findings suggest that CD8 cells suppressing HIV replication in infected individuals may be critical in preventing the establishment of infection by other strains of HIV by blocking virus replication.

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1996-12-01
2024-03-28
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References

  1. Barker E., Mackewicz C. E., Levy J. A. 1995; Effects of TH1 and TH2 cytokines on CD8+ cell response against human immunodeficiency virus: implications for long-term survival. Proceedings of the National Academy of Sciences, USA 92:11135–11139
    [Google Scholar]
  2. Brinchmann J. E., Gaudernack G., Vartdal F. 1990; CD8+ T cells inhibit HIV replication in naturally infected CD4+ T cells: evidence for a soluble inhibitor. Journal of Immunology 144:2961–2966
    [Google Scholar]
  3. Brinchmann J. E., Albert J., Vartdal F. 1991; Few infected CD4+ T cells but a high proportion of replication-competent provirus copies in asymptomatic human immunodeficiency virus type 1 infection. Journal of Virology 65:2019–2023
    [Google Scholar]
  4. Castro B. A., Weiss C. D., Wiviott L. D., Levy J. A. 1988; Optimal conditions for recovery of the human immunodeficiency virus from peripheral blood mononuclear cells. Journal of Clinical Microbiology 26:2371–2376
    [Google Scholar]
  5. Castro B. A., Barnett S. W., Evans L. A., Moreau J., Odehouri K., Levy J. A. 1990; Biologic heterogeneity of human immunodeficiency virus type 2 (HIV-2). Virology 178:527–534
    [Google Scholar]
  6. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P. 1995; Identification of RANTES, MIP-lalpha, and MIP- lbeta as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811–1815
    [Google Scholar]
  7. Evans L. A., McHugh T. M., Stites D. P., Levy J. A. 1987; Differential ability of human immunodeficiency virus isolates to productively infect human cells. Journal of Immunology 138:3415–3418
    [Google Scholar]
  8. Gao F., Yue L., Robertson D. L., Hill S. C., Hui H., Biggar R. J., Neequaye A. E., Whelan T. M., Ho D. D., Shaw G. M., Sharp P. M., Hahn B. H. 1994; Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology. Journal of Virology 68:7433–7447
    [Google Scholar]
  9. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. 1986; Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proceedings of the National Academy of Sciences, USA 83:772–776
    [Google Scholar]
  10. Hoffman A. D., Banapour B., Levy J. A. 1985; Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions. Virology 147:326–335
    [Google Scholar]
  11. Hoxie J. A., Alpers J. D., Rackowski J. L., Huebner K., Haggarty B. S., Cedarbaum A. J., Reed J. C. 1986; Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. Science 234:1123–1127
    [Google Scholar]
  12. Kannagi M., Masuda T., Hattori T., Kanoh T., Nasu K., Yamamoto N., Harada S. 1990; Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro . Journal of Virology 64:3399–3406
    [Google Scholar]
  13. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
    [Google Scholar]
  14. Landay A. L., Mackewicz C., Levy J. A. 1993; An activated CD8+ T cell phenotype correlates with anti-HIV activity and asymptomatic clinical status. Clinical Immunology and Immunopathology 69:106–116
    [Google Scholar]
  15. LeGuern M., Levy J. A. 1992; HIV-1 can superinfect HIV-2-infected cells: pseudotype virions produced with expanded cellular host range. Proceedings of the National Academy of Sciences, USA 89:363–367
    [Google Scholar]
  16. Leonard G., Chaput A., Courgnaud V., Sangare A., Denis F., Brechot C. 1993; Characterization of dual HIV-1 and HIV-2 serological profiles by polymerase chain reaction. AIDS 7:1185–1189
    [Google Scholar]
  17. Levy J. A. 1993; HIV pathogenesis and long-term survival. AIDS 7:1401–1410
    [Google Scholar]
  18. Levy J. A. 1994 HIV and the Pathogenesis of AIDS Washington, DC: American Society for Microbiology;
    [Google Scholar]
  19. Levy J. A., Shimabukuro J. 1985; Recovery of AIDS-associated retroviruses from patients with AIDS or AIDS-related conditions, and from clinically healthy individuals. Journal of Infectious Diseases 152:734–738
    [Google Scholar]
  20. Levy J. A., Tobler L. H., McHugh T. M., Casavant C. H., Stites D. P. 1985; Long-term cultivation of T cells subsets from patients with acquired immune deficiency syndrome. Clinical Immunology and Immuno- pathology 35:328–336
    [Google Scholar]
  21. Levy J. A., Mackewicz C. E., Barker E. 1996; Controlling HIV pathogenesis: the role of noncytotoxic anti-HIV activity of CD8+ cells. Immunology Today 17:217–224
    [Google Scholar]
  22. Mackewicz C. E., Levy J. A. 1992; CD8+ cell anti-HIV activity: nonlytic suppression of virus replication. AIDS Research and Human Retroviruses 8:1039–1050
    [Google Scholar]
  23. Mackewicz C. E., Ortega H. W., Levy J. A. 1991; CD8+ cell anti- HIV activity correlates with the clinical state of the infected individual. Journal of Clinical Investigation 87:1462–1466
    [Google Scholar]
  24. Mackewicz C. E., Blackbourn D. J., Levy J. A. 1995; CD8+ cells suppress HIV replication by inhibiting viral transcription. Proceedings of the National Academy of Sciences, USA 92:2308–2312
    [Google Scholar]
  25. Mackewicz C. E., Barker E., Orque R., Levy J. A. 1996; CD8+ T cell-mediated suppression of HIV replication: relevance of known chemokines and other cytokines. XI International Conference on AIDS 1:226
    [Google Scholar]
  26. McNearney T., Hornickova Z., Markham R., Birdwell A., Arens M., Saah A., Ratner L. 1992; Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease. Proceedings of the National Academy of Sciences, USA 89:10247–10251
    [Google Scholar]
  27. Meyerhans A., Vartanian J. P., Hultgren C., Plikat U., Karisson A., Wang L., Erikkson S., Wain-Hobson S. 1994; Restriction and enhancement of human immunodeficiency virus type 1 replication by modulation of intracellular deoxynucleoside triphosphate pools. Journal of Virology 68:535–540
    [Google Scholar]
  28. Oravecz T., Pall M., Norcross M. A. 1996; β-Chemokine inhibition of monocytotropic HIV-1 infection. Interference with a postbinding fusion step. Journal of Immunology 157:1329–1332
    [Google Scholar]
  29. Pan L. Z., Cheng-Mayer C., Levy J. A. 1987; Patterns of antibody response in individuals infected with the human immunodeficiency virus. Journal of Infectious Diseases 155:626–632
    [Google Scholar]
  30. Psallidopoulos M. C., Schnittman S. M., Thompson L. M. III, Baseler M., Fauci A. S., Lane H. C., Salzman N. P. 1989; Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals. Journal of Virology 63:4626–4631
    [Google Scholar]
  31. Putkonen P., Walther L., Zhang Y. Z., Li S. L., Nilsson C., Albert J., Biberfeld P., Thorstensson R., Biberfeld G. 1995; Long-term protection against SIV-induced disease in macaques vaccinated with a live attenuated HIV-2 vaccine. Nature Medicine 1:914–918
    [Google Scholar]
  32. Robertson D. L., Sharp P. M., McCutchan F. E., Hahn B. H. 1995; Recombination in HIV-1. Nature 374:124–126
    [Google Scholar]
  33. Salmon P., Olivier R., Riviere Y., Brisson E., Gluckman J.-C, Kieny M.-P., Montagnier L., Klatzmann D. 1988; Loss of CD4 membrane expression and CD4 mRNA during acute human immunodeficiency virus replication. Journal of Experimental Medicine 168:1953–1969
    [Google Scholar]
  34. Shirazi Y., Pitha P. M. 1992; Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. Journal of Virology 66:1321–1328
    [Google Scholar]
  35. Shirazi Y., Pitha P. M. 1993; Interferon alpha-mediated inhibition of human immunodeficiency virus type 1 provirus synthesis in T-cells. Virology 193:303–312
    [Google Scholar]
  36. Taddeo B., Federico M., Titti F., Rossi G. B., Verani P. 1993; Homologous superinfection of both producer and nonproducer HIV- infected cells is blocked at a late retrotranscription step. Virology 194:441–452
    [Google Scholar]
  37. Tang S., Patterson B., Levy J. A. 1995; Highly purified quiescent human peripheral blood CD4+ T cells are infectible by human immunodeficiency virus but do not release virus after activation. Journal of Virology 69:5659–5665
    [Google Scholar]
  38. Tateno M., Levy J. A. 1988; MT-4 plaque formation can distinguish cytopathic subtypes of the human immunodeficiency virus (HIV). Virology 167:299–301
    [Google Scholar]
  39. Towbin H., Staehelin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences, USA 76:4350–4355
    [Google Scholar]
  40. Travers K., Mboup S., Marlink R., Gueye-Ndiaye A., Siby T., Thior I., Traore I., Dieng-Sarr A., Sankale J.-L., Mullins C., Ndoye I., Hsieh C. C., Essex M., Kanki P. 1995; Natural protection against HIV-1 infection provided by HIV-2. Science 268:1612–1615
    [Google Scholar]
  41. Tremblay M., Numazaki K., Li X. G., Gornitsky M., Hiscott J., Wainberg M. A. 1990; Resistance to infection by HIV-1 of peripheral blood mononuclear cells from HIV-l-infected patients is probably mediated by neutralizing antibodies. Journal of Immunology 145:2896–2901
    [Google Scholar]
  42. Tsubota H., Lord C. I., Watkins D. I., Morimoto C., Letvin N. L. 1989; A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. Journal of Experimental Medicine 169:1421–1434
    [Google Scholar]
  43. Volsky D. J., Simm M., Shahabuddin M., Li G., Chao W., Potash M.J. 1996; Interference to human immunodeficiency virus type 1 infection in the absence of downmodulation of the principal virus receptor, CD4. Journal of Virology 70:3823–3833
    [Google Scholar]
  44. Walker B. D., Plata F. 1990; Cytotoxic T lymphocytes against HIV. AIDS 4:177–184
    [Google Scholar]
  45. Walker C. M., Moody D. J., Stites D. P., Levy J. A. 1986; CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 234:1563–1566
    [Google Scholar]
  46. Walker C. M., Erikson A. L., Hsueh F. C., Levy J. A. 1991a; Inhibition of human immunodeficiency virus replication in acutely infected CD4+ cells by CD8+ cells involves a noncytotoxic mechanism. Journal of Virology 65:5921–5927
    [Google Scholar]
  47. Walker C. M., Thomson-Honnebier G. A., Hsueh F. C., Erickson A. L., Pan L.-Z., Levy J. A. 1991b; CD8+ T cells from HIV-l-infected individuals inhibit acute infection by human and primate immunodeficiency viruses. Cellular Immunology 137:420–428
    [Google Scholar]
  48. Werner A., Levy J. A. 1993; Human immunodeficiency virus type 1 envelope gp120 is cleaved after incubation with recombinant soluble CD4. Journal of Virology 67:2566–2574
    [Google Scholar]
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