Transcription of Human Immunodeficiency Virus Promoter in CNS-Derived Cells: Effect of TAT on Expression of Viral and Cellular Genes

  • Kamel Khalili
  • J. Paul Taylor
  • Crystina Cupp
  • Michael Zeira
  • Shohreh Amini

Abstract

Approximately 60% of patients with AIDS have neurologic symptoms, the so-called AIDS-related subacute encephalopathy, and more than 80% are found to have neuropathologic abnormalities at autopsy.1,2 The most common neurologic problems include: toxoplasmosis, cryptococcosis, primary lymphoma of the central nervous system (CNS), and subacute encephalitis or AIDS encephalopathy. 3–8 Histologic analysis of CNS tissues from AIDS patients shows enlargement of oligodendrocytes and formation of multinucleated giant cells.9–17 The detection of HIV DNA in the brain and recovery of infectious virus particles from cerebrospinal fluid and brain tissue of patients with AIDS have suggested that HIV-1 may be directly responsible for some of the neurologic deficits found in these patients.18–22 The presence of CD4, the high-affinity receptor for HIV-1 in human brain tissue and in certain glioma cell lines, has been reported.23,24 Furthermore, HIV 1 has been shown to infect glial cells in vitro and has been detected in oligodendrocytes and astroglial cells in vivo. 18, 23, 25–28 Together, these observations indicate that HIV-1 is not only lymphotropic but also neurotropic.However, the exact mechanisms involved in the neuropathogenesis of HIV-1 and AIDS dementia complex remain unclear. A simple model would envisage the direct infection of neurons and glia by neurotropic HIV-1 that results in indirect or direct cytotoxicity mediated by cytotoxic T cells. Alternatively, infection of monocytic macrophages with HIV-1 may lead to the release of a diffusible inflammatory component(s) that destroys neighboring neural cells, and/or results in the release of cytokines which are toxic to neural cells. Moreover, other neurotropic viruses, JCV and cytomegalovirus (CMV) may act as cofactors in the pathogenesis of AIDS-related neurologic disorders.

Keywords

Glycerol Phenol Lymphoma Dementia Polypeptide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R. Lechtenberg, and J.H. Sher. “AIDS in the Nervous System,” Churchill Livingstone, New York.Google Scholar
  2. 2.
    B.A.Navia,E.S.Cho,C.K.Petito, and R.W. Price. The AIDS dementia complex: II. Neuropathology. Ann. Neurol. 19:525 (1986).PubMedCrossRefGoogle Scholar
  3. 3.
    L.G. Epstein, L.R. Sharer, V.V. Joshi, M.M. Fojas, and M.R. Koenigsberger. Progressive encephalopathy in children with acquired immune deficiency syndrome. Ann. Neurol. 17:488(1985).PubMedCrossRefGoogle Scholar
  4. 4.
    J.L. Ho, P. Poldre, and D. McEniry. Acquired immunodeficiency syndrome with progressive multifocal leukoencephalopathy and monoclonal B-cell proliferation. Ann. Intern Med. 100:693 (1984).PubMedGoogle Scholar
  5. 5.
    B.A. Navia, and R.W. Price. The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection. Arch. Neurol. 44:65 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    R.W. Price, B.J. Brew, and M.K. Rosenblum. The AIDS dementia complex and HIV-1 brain infection: a pathologic model of virus-immune interaction. Research Publications: Association for Research in Nervous and Mental Disease 68:269 (1990).Google Scholar
  7. 7.
    R.W. Price, B. Brew, J. Sidtis, et al. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586 (1988).PubMedCrossRefGoogle Scholar
  8. 8.
    M.K.Rosenblum. Infection of the central nervous system by the human immunodeficiency virus type I. Pathol. Ann. 25:117 (1990).Google Scholar
  9. 9.
    J. Bedri, W. Weinstein, P. DiGregorio, and M.A. Verity. Progressive multifocal leukoencephalopathy in acquired immune deficiency syndrome. N. Engl. J. Med. 309:492 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    J.R. Berger, L. Moskowitz, M. Fischer, and R.E. Kelly. The neurological complications of AIDS, frequently the initial manifestation. Neurology 34:134(1984).Google Scholar
  11. 11.
    L.W. Blum, R.A. Chambers, R.J. Schwartzman, and L. Streletz. Progressive multifocal leukoencephalopathy in acquired immune deficiency syndrome. Arch. Neurol. 42:137 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    B.R. Brook, and D.L. Walker. Progressive multifocal leukoencephalopathy. Neurol. Clin. 2:299 (1984).Google Scholar
  13. 13.
    J.D. England, Y. Hsu, P. Garen, J. Goust, and P. Biggs. Progressive multifocal leukoencephalopathy with the acquired immune deficiency syndrome. South,. Med. J. 77:1041 (1984).CrossRefGoogle Scholar
  14. 14.
    L.B. Krupp, H. Lipton, M. Swerdlow, N. Leeds, and J. Liena. Progressive multifocal leukoencephalopathy: clinical and radiographic features. Ann. Neurol. 17:344 (1985).PubMedCrossRefGoogle Scholar
  15. 15.
    J.R. Miller, R. Barrett, C. Britton, et al. Progressive multifocal leukoencephalopathy in a male homosexual with T-cell immune deficiency. N. Engl. J. Med. 307:1436 (1982).PubMedCrossRefGoogle Scholar
  16. 16.
    W.D. Snider, D.M. Simpson, S. Neilson, et al. Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann. Neurol. 14:403(1983).PubMedCrossRefGoogle Scholar
  17. 17.
    J.D. Speelman, J. ter Schegget, G. Bots, J. Stam, and B.Verbeeten. Progressive multifocal leukoencephalopathy in a case of acquired immune deficiency syndrome. Clin. Neurol. Neurosurg. 87:27 (1985).PubMedCrossRefGoogle Scholar
  18. 18.
    F. Gyorkey, J.L. Melnick, and P.Gyorkey. Human immunodeficiency virus in brain biopsies of patients with AIDS and progressive encephalopathy. J. Infect. Dis. 155:870(1987).PubMedCrossRefGoogle Scholar
  19. 19.
    D.D. Ho, T.R. Rota, R.T. Schooley, et al. Isolation of HTLV-III from cerebrospinal fluid and tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N.Engl. J. Med. 313:1493 (1985).PubMedCrossRefGoogle Scholar
  20. 20.
    S. Koenig, H.E. Gendelman, J.M. Orenstein, et al. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233:1089 (1986).PubMedCrossRefGoogle Scholar
  21. 21.
    J.A. Levy, J. Shimabukuro, H. Hollander, J. Mills, and L. Kaminsky. Isolation of AIDS-associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet 2:586 (1985).PubMedGoogle Scholar
  22. 22.
    S. Pang, Y. Koyanagi, S. Miles, et al. High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature 343:85 (1990).PubMedCrossRefGoogle Scholar
  23. 23.
    S. Dewhurst, K. Sakai, J. Bresser, et al. Persistent productive infection of human glial cells by human immunodeficiency virus (HIV) and by infectious molecular clones of HIV. J. Virol. 61:3774 (1987).PubMedGoogle Scholar
  24. 24.
    C.Tornatore, A. Nath, K. Amemiya, and E.O.Major. Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta. J. Virol. 65:6094 (1991).PubMedGoogle Scholar
  25. 25.
    J. Michaels, L.R. Sharer, and L.G. Epstein. Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review. Immunodeficiency Rev. 1:71 (1988).Google Scholar
  26. 26.
    R.H. Rhodes, J.M. Ward, D.L. Walker, and A.A. Ross. Progressive multifocal leukoencephalopathy and retroviral encephalitis in acquired immunodeficiency syndrome. Arch. Path. Lab. Med. 112:1207 (1988).PubMedGoogle Scholar
  27. 27.
    J.M. Ward, T.J. O’Leary, G.B. Baskin, et al. Immunohistochemical localization of human and simian immunodeficiency viral antigens in fixed tissue sections. Am. J. Path. 127:199 (1987).PubMedGoogle Scholar
  28. 28.
    C.A. Wiley, R.D. Schrier, J.A. Nelson, P.W. Lampert, and M.B. Oldstone. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc. Natl. Acad. Sci. 83:7089 (1986).PubMedCrossRefGoogle Scholar
  29. 29.
    M.B. Peterlin, and P. Luciw. Molecular biology of AIDS. AIDS 2:S29 (1988).PubMedCrossRefGoogle Scholar
  30. 30.
    B.R. Cullen. The HIV-1 Tat protein: an RNA sequence-specific processivity factor? Cell 63:655 (1990).PubMedCrossRefGoogle Scholar
  31. 31.
    B.R. Cullen, and W.C. Greene. Regulatory pathways governing HIV-1 replication. Cell 58:423 (1989).PubMedCrossRefGoogle Scholar
  32. 32.
    K.A. Jones, J.T. Kadonga, P.A. Luciw, and R. Tijan. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Spl. Science 232:755(1986).PubMedCrossRefGoogle Scholar
  33. 33.
    K. Kawakami, C. Scheidereit, and R.G. Roeder. Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro. Proc. Natl Acad. Sci. USA 85:4700 (1988).PubMedCrossRefGoogle Scholar
  34. 34.
    G. Nabel, and D. Baltimore. An inducible transcription factor activates expression of human immunodeficiency virus in T-cells. Nature 326:711 (1987).PubMedCrossRefGoogle Scholar
  35. 35.
    P.A. Bauerle. The inducible transcription activator NFkB: regulation by distinct protein subunits. Biochim. Biophys. Acta 1072:63 (1991).Google Scholar
  36. 36.
    J. Rappaport, S.-J. Lee, K. Khalili, and F. Wong-Staal. The acidic aminoterminal region of the HIV-1 Tat protein constitutes an essential activating domain,. New Biol. 1:101 (1989).PubMedGoogle Scholar
  37. 37.
    M.B. Feinberg, D. Baltimore, and A.D. Frankel. The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc. Natl. Acad. Sci. USA 88:4045 (1991).PubMedCrossRefGoogle Scholar
  38. 38.
    M.F. Laspia, A.P. Rice, and M.B. Mathews. Synergy between HIV-1 Tat and adenovirus E1 A is principally due to stabilization of transcriptional elongation. Genes Dev. 4:2397 (1990).PubMedCrossRefGoogle Scholar
  39. 39.
    M.F. Laspia, A.P. Rice, and M.B. Mathews. HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell 59:283 (1989).PubMedCrossRefGoogle Scholar
  40. 40.
    S. Calnan, S. Biancalani, D. Hudson, and A.D. Frankel. Analysis of argi-nine-rich peptides from the HIV Tat protein reveals unusual features of RNA-protein recognition. Genes Dev. 5:201 (1991).PubMedCrossRefGoogle Scholar
  41. 41.
    B.J. Calnan, B.Tidor, S. Biancalana, D. Hudson, and A.D. Frankel. Argi-nine-mediated RNA recognition: the ariginine fork. Science 252:1167 (1991).CrossRefGoogle Scholar
  42. 42.
    S. Feng, and E.C. Holland. HIV-1 Tat transactivation requires the loop sequence within TAR. Nature 334:165 (1988).PubMedCrossRefGoogle Scholar
  43. 43.
    J.A. Garcia, D. Harrich, E. Soultanakis, et al. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation. EMBO J. 8:765 (1989).PubMedGoogle Scholar
  44. 44.
    C.A. Rosen, J.G. Sodrowski, and W.A. Haseltine. The location of cis-activating regulatory sequences in the human T cell lymphotropic virus type III (HIV-III/LAV) long terminal repeat. Cell 41:813 (1985).PubMedCrossRefGoogle Scholar
  45. 45.
    R. Marciniak. Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation-response (TAR) element of human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 87:3624 (1990).PubMedCrossRefGoogle Scholar
  46. 46.
    L. Buonaguro, G. Barillari, H.K. Chang, et al. Effect of the human immunodeficiency virus type 1 tat protein on the expression of inflammatory cytokines. J. Virol. 66:7159 (1992).PubMedGoogle Scholar
  47. 47.
    K.J. Sastry, R.H.R. Reddy, R. Pandita, K. Totpal, and B.B. Aggarwal. HIV-1 tat gene induces tumor necrosis factor-β (lymphotoxin) in a human Blymphoblastoid cell line. J. Cell Chem. 265:20091 (1990).Google Scholar
  48. 48.
    J.P Taylor, C. Cupp, A.Diaz, et al. Activation of expression of genes coding for extracellular matrix proteins in tat-producing glioblastoma cells. Proc. Natl. Acad. Sci. USA 89:9617 (1992).PubMedCrossRefGoogle Scholar
  49. 49.
    R.P. Viscidi, K. Mayur, H.M. Lederman, and A.D. Frankel. Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1. Science 246:1606 (1989).PubMedCrossRefGoogle Scholar
  50. 50.
    S.M. Wahl, J.B.Allen, N. McCartney-Francis, et al. Macrophage-and astrocyte-derived transforming growth factor β as a mediator of central nervous system dysfunction in acquired immunodeficiency syndrome. J. Exp. Med. 173:981 (1991).PubMedCrossRefGoogle Scholar
  51. 51.
    C. Cupp, J.P. Taylor, K. Khalili, and S. Amini. Evidence of stimulation of the transforming growth factor (β-1 promoter by HIV-1 Tat in cells derived from CNS. Oncogene 8:2231 (1993).PubMedGoogle Scholar
  52. 52.
    A. Adachi, H. Gendelman, S. Koenig, et al. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J. Virol. 59:284 (1986).PubMedGoogle Scholar
  53. 53.
    C.M. Gorman, L.F. Moffat, and B.H., Howard. Recombinant genomes which express chloramphenicol acetyl transferase in mammalian cells. Mol. Cell. Biol. 2:1044(1982).PubMedGoogle Scholar
  54. 54.
    F.L.Graham, and A.J. van der Eb. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456 (1973).PubMedCrossRefGoogle Scholar
  55. 55.
    C. Queen, and D. Baltimore, immunoglobulin gene transcription is activated by downstream sequence elements. Cell 33:586 (1988).Google Scholar
  56. 56.
    F. Ausubel, R. Brent, R.E. Kingston, et al. “Current Protocols in Molecular Biology,” John Wiley&Sons, Inc., New York (1989).Google Scholar
  57. 57.
    E.O. Major, K. Amemiya, C.S. Tornatore, S.A. Houff, and J.R. Berger. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin. Microbiol. Rev. 5:49 (1992).PubMedGoogle Scholar
  58. 58.
    G.M. ZuRhein. Polyoma-like virions in a human demyelinating disease. Acta Neuropathol. (Berl.) 8:57 (1967).CrossRefGoogle Scholar
  59. 59.
    C.A. Wiley, M. Grafe, C. Kennedy, and J.A. Nelson. Human immunodeficiency virus (HIV) and JC virus in acquired immune deficiency syndrome (AIDS) patients with progressive multifocal leukoencephalopathy. Acta Neuropathol. 76:338 (1988).PubMedCrossRefGoogle Scholar
  60. 60.
    H. Tada, J. Rappaport, M. Lashgari, et al. Transactivation of the JC virus late promoter by the Tat protein of type 1 human immunodeficiency virus in glial cells. Proc Natl. Acad. Sci. USA 87:3479 (1990).PubMedCrossRefGoogle Scholar
  61. 61.
    M. Chowdhury, J.P, Taylor, H. Tada, et al. Regulation of the human neurotropic virus promoter by JCV-T antigen and HIV-1 Tat protein. Oncogene 5:1737 (1970),Google Scholar
  62. 62.
    M. Chowdhury, J.P. Taylor, C. F. Chang, J. Rappaport, and K. Khalili. Evidence that a sequence similar to TAR is important for induction of the JC virus late promoter by human immunodeficiency virus type 1 Tat. J. Virol. 66:7355(1992).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Kamel Khalili
    • 1
  • J. Paul Taylor
    • 1
  • Crystina Cupp
    • 1
  • Michael Zeira
    • 1
  • Shohreh Amini
    • 1
  1. 1.Molecular Neurovirology Section Jefferson Institute of Molecular MedicineThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations