1887

Abstract

To test the anti-simian immunodeficiency virus (SIV) efficacy of interferon (IFN)-β-engineered lymphocytes, peripheral blood lymphocytes harvested from two uninfected macaques were transduced with a retroviral vector carrying a constitutively expressed IFN-β gene and reinfused, resulting in approximately 1 IFN-β-transduced cell out of 1000 circulating cells. The gene-modified cells were well tolerated and could be detected for at least 74 days without causing any apparent side effects. These two animals together with three untreated control macaques were then infected with SIVmac251. The two IFN-β-infused macaques are in good health, 478 days after infection, with a reduced plasma virus load and sustained numbers of CD4 and CD8 cells. Throughout the study, the proportion of IFN-β-transduced cells has been maintained. Of the three control macaques, two were characterized by a high plasma virus load and a decrease in CD4 cells. One was moribund and was sacrificed 350 days after infection and the other now has fewer than 100 circulating CD4 cells/ml. Unexpectedly, the third control macaque, which, like the two IFN-β-infused animals, had a low plasma virus load and a maintenance of CD4 and CD8 cell number, was characterized by a permanent level of serum IFN-β, of unknown origin, already present before SIV infection. Although no definite conclusion can be made in view of the limited number of animals, these data indicate that further exploration is warranted of an IFN-β-based anti-human immunodeficiency virus gene therapy.

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2000-11-01
2024-12-14
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References

  1. Baca-Regen L., Heinzinger N., Stevenson M., Gendelman H. E. 1994; Alpha interferon-induced antiretroviral activities: restriction of viral nucleic acid synthesis and progeny virion production in human immunodeficiency virus type 1-infected monocytes. Journal of Virology 68:7559–7565
    [Google Scholar]
  2. Baltimore D. 1988; Gene therapy. Intracellular immunization. Nature 335:395–396
    [Google Scholar]
  3. Belardelli F. 1995; Role of interferons and other cytokines in the regulation of the immune response. APMIS 103:161–179
    [Google Scholar]
  4. Cheret A., Le Grand R., Caufour P., Dereuddre-Bosquet N., Matheux F., Neildez O., Theodoro F., Maestrali N., Benveniste O., Vaslin B., Dormont D. 1996; Cytokine mRNA expression in mononuclear cells from different tissues during acute SIVmac251 infection of macaques. AIDS Research and Human Retroviruses 12:1263–1272
    [Google Scholar]
  5. Clerici M., Shearer G. M. 1994; The Th1–Th2 hypothesis of HIV infection: new insights. Immunology Today 15:575–581
    [Google Scholar]
  6. Coccia E. M., Krust B., Hovanessian A. G. 1994; Specific inhibition of viral protein synthesis in HIV-infected cells in response to interferon treatment. Journal of Biological Chemistry 269:23087–23094
    [Google Scholar]
  7. Cremer I., Vieillard V., De Maeyer E. 2000; Retrovirally mediated IFN-β transduction of macrophages induces resistance to HIV, correlated with up-regulation of RANTES production and down-regulation of C-C chemokine receptor-5 expression. Journal of Immunology 164:1582–1587
    [Google Scholar]
  8. Daniel M. D., Letvin N. L., King N. W., Kannagi M., Sehgal P. K., Hunt R. D., Kanki P. J., Essex M., Desrosiers R. C. 1985; Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Science 228:1201–1204
    [Google Scholar]
  9. De Maeyer E., De Maeyer-Guignard J. 1988 Interferons and Other Regulatory Cytokines New York: John Wiley;
  10. Desrosiers R. C. 1990; The simian immunodeficiency viruses. Annual Review of Immunology 8:557–578
    [Google Scholar]
  11. Erhart M. A., Piller K., Weaver S. 1989; Polymorphism and gene conversion in mouse α-globin haplotypes. Genetics 115:511–519
    [Google Scholar]
  12. Fall L. S., M′Bika J. P., Le Coq H., Fouchard M., Astgen A., Bizzini B., Gringeri A., Santagostino E., Burny A., Zagury D., Chams C. 1995; Biological effect of active anti-IFN-α immunization in HIV-infected patients. Biomedicine & Pharmacotherapy 49:422–428
    [Google Scholar]
  13. Hadida F., De Maeyer E., Cremer I., Autran B., Baggiolini M., Debré P., Vieillard V. 1999; Acquired constitutive expression of interferon beta after gene transduction enhances human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity by a RANTES-dependent mechanism. Human Gene Therapy 10:1803–1810
    [Google Scholar]
  14. Hansen B. D., Nara P. L., Maheshwari R. K., Sidhu G. S., Bernbaum J. G., Hoekzema D., Meltzer M. S., Gendelman H. E. 1992; Loss of infectivity by progeny virus from alpha interferon-treated human immunodeficiency virus type 1-infected T cells is associated with defective assembly of envelope gp120. Journal of Virology 66:7543–7548
    [Google Scholar]
  15. Jin X., Bauer D. E., Tuttleton S. E., Lewin S., Gettie A., Blanchard J., Irwin C. E., Safrit J. T., Mittler J., Weinberger L., Kostrikis L. G., Zhang L., Perelson A. S., Ho D. D. 1999; Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques. Journal of Experimental Medicine 189:991–998
    [Google Scholar]
  16. Kornbluth R. S., Oh P. S., Munis J. R., Cleveland P. H., Richman D. D. 1990; The role of interferons in the control of HIV replication in macrophages. Clinical Immunology & Immunopathology 54:200–219
    [Google Scholar]
  17. Lauret E., Vieillard V., Rousseau V., De Maeyer-Guignard J., De Maeyer E. 1994; Exploring interferon beta for gene therapy of HIV infection. Research in Immunology 145:674–677
    [Google Scholar]
  18. Le Grand R., Clayette P., Noack O., Vaslin B., Theodoro F., Michel G., Roques P., Dormont D. 1994; An animal model for antilentiviral therapy: effect of zidovudine on viral load during acute infection after exposure of macaques to simian immunodeficiency virus. AIDS Research and Human Retroviruses 10:1279–1287
    [Google Scholar]
  19. Lehner T., Wang Y., Cranage M., Bergmeier L. A., Mitchell E., Tao L., Hall G., Dennis M., Cook N., Brookes R., Klavinskis L., Jones I., Doyle C., Ward R. 1996; Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques. Nature Medicine 2:767–775
    [Google Scholar]
  20. Matheux F., Le Grand R., Rousseau V., De Maeyer E., Dormont D., Lauret E. 1999; Macaque lymphocytes transduced by a constitutively expressed interferon beta gene display an enhanced resistance to SIVmac251 infection. Human Gene Therapy 10:429–440
    [Google Scholar]
  21. Michael N. L. 1999; Host genetic influences on HIV-1 pathogenesis. Current Opinion in Immunology 11:466–474
    [Google Scholar]
  22. Minagawa T., Mizuno K., Hirano S., Asano M., Numata A., Kohanawa M., Nakane A., Hachimori K., Tamagawa S., Negishi M. and others 1989; Detection of high levels of immunoreactive human beta-1 interferon in sera from HIV-infected patients. Life Sciences 45:iii–vii
    [Google Scholar]
  23. Pantaleo G. 1997; How immune-based interventions can change HIV therapy. Nature Medicine 3:483–486
    [Google Scholar]
  24. Piscitelli S. C., Minor J. R., Saville M. W., Davey R. T.Jr(1996; Immune-based therapies for treatment of HIV infection. Annals of Pharmacotherapy 30:62–76
    [Google Scholar]
  25. Poli G., Orenstein J. M., Kinter A., Folks T. M., Fauci A. S. 1989; Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science 244:575–577
    [Google Scholar]
  26. Schmitz J. E., Kuroda M. J., Santra S., Sasseville V. G., Simon M. A., Lifton M. A., Racz P., Tenner-Racz K., Dalesandro M., Scallon B. J., Ghrayeb J., Forman M. A., Montefiori D. C., Rieber E. P., Letvin N. L., Reimann K. A. 1999; Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283:857–860
    [Google Scholar]
  27. 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]
  28. Tough D. F., Borrow P., Sprent J. 1996; Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272:1947–1950
    [Google Scholar]
  29. Vieillard V., Lauret E., Rousseau V., De Maeyer E. 1994; Blocking of retroviral infection at a step prior to reverse transcription in cells transformed to constitutively express interferon beta. Proceedings of the National Academy of Sciences, USA 91:2689–2693
    [Google Scholar]
  30. Vieillard V., Lauret E., Maguer V., Jacomet C., Rozenbaum W., Gazzolo L., De Maeyer E. 1995; Autocrine interferon-beta synthesis for gene therapy of HIV infection: increased resistance to HIV-1 in lymphocytes from healthy and HIV-infected individuals. AIDS 9:1221–1228
    [Google Scholar]
  31. Vieillard V., Cremer I., Lauret E., Rozenbaum W., Debre P., Autran B., De Maeyer E. 1997; Interferon beta transduction of peripheral blood lymphocytes from HIV-infected donors increases Th1-type cytokine production and improves the proliferative response to recall antigens. Proceedings of the National Academy of Sciences, USA 94:11595–11600
    [Google Scholar]
  32. Vieillard V., Jouveshomme S., Leflour N., Jean-Pierre E., Debre P., De Maeyer E., Autran B. 1999; Transfer of human CD4+ T lymphocytes producing beta interferon in Hu-PBL-SCID mice controls human immunodeficiency virus infection. Journal of Virology 73:10281–10288
    [Google Scholar]
  33. Wang Y., Tao L., Mitchell E., Bogers W. M. J. M., Doyle C., Bravery C. A., Bergmeier L. A., Kelly C. G., Heeney J. L., Lehner T. 1998; Generation of CD8 suppressor factor and β chemokines, induced by xenogeneic immunization, in the prevention of simian immunodeficiency virus infection in macaques. Proceedings of the National Academy of Sciences, USA 95:5223–5228
    [Google Scholar]
  34. Zhang L., He T., Huang Y., Chen Z., Guo Y., Wu S., Kunstman K. J., Brown R. C., Phair J. P., Neumann A. U., Ho D. D., Wolinsky S. M. 1998; Chemokine coreceptor usage by diverse primary isolates of human immunodeficiency virus type 1. Journal of Virology 72:9307–9312
    [Google Scholar]
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