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. 1996 Sep;70(9):6502–6507. doi: 10.1128/jvi.70.9.6502-6507.1996

Resistance of chimpanzee T cells to human immunodeficiency virus type 1 Tat-enhanced oxidative stress and apoptosis.

A Ehret 1, M O Westendorp 1, I Herr 1, K M Debatin 1, J L Heeney 1, R Frank 1, P H Krammer 1
PMCID: PMC190688  PMID: 8709290

Abstract

CD4+ T-cell depletion in AIDS patients involves induction of apoptosis in human immunodeficiency virus (HIV)-infected and noninfected T cells. The HIV type 1 (HIV-1)-transactivating protein Tat enhances apoptosis and activation-induced cell death (AICD) of human T cells. This effect is mediated by the CD95 (APO-1/Fas) receptor-CD95 ligand (CD95L) system and may be linked to the induction of oxidative stress by Tat. Here we show that HIV-1 Tat-induced oxidative stress is necessary for sensitized AICD in T cells caused by CD95L expression. Tat-enhanced apoptosis and CD95L expression in T cells are inhibited by neutralizing anti-Tat antibodies, antioxidants, and the Tat inhibitor Ro24-7429. Chimpanzees infected with HIV-1 show viral replication resembling early infection in humans but do not show T-cell depletion or progression towards AIDS. The cause for this discrepancy is unknown. Here we show that unlike Tat-treated T cells in humans, Tat-treated chimpanzee T cells do not show downregulation of manganese superoxide dismutase or signs of oxidative stress. Chimpanzee T cells are also resistant to Tat-enhanced apoptosis, AICD, and CD95L upregulation.

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Selected References

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  1. Banda N. K., Bernier J., Kurahara D. K., Kurrle R., Haigwood N., Sekaly R. P., Finkel T. H. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J Exp Med. 1992 Oct 1;176(4):1099–1106. doi: 10.1084/jem.176.4.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braddock M., Cannon P., Muckenthaler M., Kingsman A. J., Kingsman S. M. Inhibition of human immunodeficiency virus type 1 Tat-dependent activation of translation in Xenopus oocytes by the benzodiazepine Ro24-7429 requires trans-activation response element loop sequences. J Virol. 1994 Jan;68(1):25–33. doi: 10.1128/jvi.68.1.25-33.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Debatin K. M., Fahrig-Faissner A., Enenkel-Stoodt S., Kreuz W., Benner A., Krammer P. H. High expression of APO-1 (CD95) on T lymphocytes from human immunodeficiency virus-1-infected children. Blood. 1994 May 15;83(10):3101–3103. [PubMed] [Google Scholar]
  5. Dhein J., Walczak H., Bäumler C., Debatin K. M., Krammer P. H. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) Nature. 1995 Feb 2;373(6513):438–441. doi: 10.1038/373438a0. [DOI] [PubMed] [Google Scholar]
  6. Dröge W., Murthy K. K., Stahl-Hennig C., Hartung S., Plesker R., Rouse S., Peterhans E., Kinscherf R., Fischbach T., Eck H. P. Plasma amino acid dysregulation after lentiviral infection. AIDS Res Hum Retroviruses. 1993 Sep;9(9):807–809. doi: 10.1089/aid.1993.9.807. [DOI] [PubMed] [Google Scholar]
  7. Finkel T. H., Tudor-Williams G., Banda N. K., Cotton M. F., Curiel T., Monks C., Baba T. W., Ruprecht R. M., Kupfer A. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat Med. 1995 Feb;1(2):129–134. doi: 10.1038/nm0295-129. [DOI] [PubMed] [Google Scholar]
  8. Flores S. C., Marecki J. C., Harper K. P., Bose S. K., Nelson S. K., McCord J. M. Tat protein of human immunodeficiency virus type 1 represses expression of manganese superoxide dismutase in HeLa cells. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7632–7636. doi: 10.1073/pnas.90.16.7632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goudsmit J., Smit L., Krone W. J., Bakker M., van der Noordaa J., Gibbs C. J., Epstein L. G., Gajdusek D. C. IgG response to human immunodeficiency virus in experimentally infected chimpanzees mimics the IgG response in humans. J Infect Dis. 1987 Feb;155(2):327–331. doi: 10.1093/infdis/155.2.327. [DOI] [PubMed] [Google Scholar]
  10. Gougeon M. L. Does apoptosis contribute to CD4 T cell depletion in human immunodeficiency virus infection ? Cell Death Differ. 1995 Jan;2(1):1–8. [PubMed] [Google Scholar]
  11. Gougeon M. L., Garcia S., Heeney J., Tschopp R., Lecoeur H., Guetard D., Rame V., Dauguet C., Montagnier L. Programmed cell death in AIDS-related HIV and SIV infections. AIDS Res Hum Retroviruses. 1993 Jun;9(6):553–563. doi: 10.1089/aid.1993.9.553. [DOI] [PubMed] [Google Scholar]
  12. Heeney J. L. AIDS: a disease of impaired Th-cell renewal? Immunol Today. 1995 Nov;16(11):515–520. doi: 10.1016/0167-5699(95)80043-3. [DOI] [PubMed] [Google Scholar]
  13. Heeney J., Jonker R., Koornstra W., Dubbes R., Niphuis H., Di Rienzo A. M., Gougeon M. L., Montagnier L. The resistance of HIV-infected chimpanzees to progression to AIDS correlates with absence of HIV-related T-cell dysfunction. J Med Primatol. 1993 Feb-May;22(2-3):194–200. [PubMed] [Google Scholar]
  14. Hsu M. C., Dhingra U., Earley J. V., Holly M., Keith D., Nalin C. M., Richou A. R., Schutt A. D., Tam S. Y., Potash M. J. Inhibition of type 1 human immunodeficiency virus replication by a tat antagonist to which the virus remains sensitive after prolonged exposure in vitro. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6395–6399. doi: 10.1073/pnas.90.14.6395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Katsikis P. D., Wunderlich E. S., Smith C. A., Herzenberg L. A., Herzenberg L. A. Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals. J Exp Med. 1995 Jun 1;181(6):2029–2036. doi: 10.1084/jem.181.6.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Li C. J., Friedman D. J., Wang C., Metelev V., Pardee A. B. Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. Science. 1995 Apr 21;268(5209):429–431. doi: 10.1126/science.7716549. [DOI] [PubMed] [Google Scholar]
  17. McCord J. M., Fridovich I. The utility of superoxide dismutase in studying free radical reactions. I. Radicals generated by the interaction of sulfite, dimethyl sulfoxide, and oxygen. J Biol Chem. 1969 Nov 25;244(22):6056–6063. [PubMed] [Google Scholar]
  18. Peter M. E., Dhein J., Ehret A., Hellbardt S., Walczak H., Moldenhauer G., Krammer P. H. APO-1 (CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines. Int Immunol. 1995 Nov;7(11):1873–1877. doi: 10.1093/intimm/7.11.1873. [DOI] [PubMed] [Google Scholar]
  19. Schuitemaker H., Meyaard L., Kootstra N. A., Dubbes R., Otto S. A., Tersmette M., Heeney J. L., Miedema F. Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants. J Infect Dis. 1993 Nov;168(5):1140–1147. doi: 10.1093/infdis/168.5.1140. [DOI] [PubMed] [Google Scholar]
  20. Terai C., Kornbluth R. S., Pauza C. D., Richman D. D., Carson D. A. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J Clin Invest. 1991 May;87(5):1710–1715. doi: 10.1172/JCI115188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Westendorp M. O., Frank R., Ochsenbauer C., Stricker K., Dhein J., Walczak H., Debatin K. M., Krammer P. H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995 Jun 8;375(6531):497–500. doi: 10.1038/375497a0. [DOI] [PubMed] [Google Scholar]
  22. Westendorp M. O., Shatrov V. A., Schulze-Osthoff K., Frank R., Kraft M., Los M., Krammer P. H., Dröge W., Lehmann V. HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state. EMBO J. 1995 Feb 1;14(3):546–554. doi: 10.1002/j.1460-2075.1995.tb07030.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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