HIV-1 Coat Protein GP120 Induces Neuronal Injury to Cultured Dopamine Cells

  • Barbara A. Bennett
  • Daniel E. Rusyniak
  • Charlotte K. Hollingsworth
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

Human immunodeficiency virus (HIV)-1 infection is commonly associated with neurological manifestations that can produce devastating cognitive and motor impairments.1–4 Concomitant with this are CNS disturbances which can include various organic mental disorders.5 These CNS disturbances may occur in the absence of opportunistic infections as well as in the absence of direct infection of neurons by HIV-1.4 In fact, HIV-1 has only been demonstrated in macrophage or microglial cells and not in neurons.6–9 Previous studies have shown that infection with HIV-1 results in neurotoxicity which can be elicited by viral particles, the most likely of which is the glycoprotein, gp120.10–12 This viral protein has been shown to produce neurotoxicity at very low concentrations (pM) in various neuronal culture systems10–19 as well as modify astrocyte function.20–22 The mechanism(s) by which gp 120 induces neurotoxicity are not understood, but there is evidence that NMDA receptors, Ca2+ channels, and nitric oxide (NO) are important mediators.11,13–15,18,19

Keywords

Human Immunodeficiency Virus Nitric Oxide Synthetase Process Length Organic Mental Disorder Envelope Glycoprotein Gp120 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J.C. Ameisen and A. Capron, Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis, Immunol. Today 12:102–104 (1991).PubMedCrossRefGoogle Scholar
  2. 2.
    J. Artigas, F. Niedobitek, G. Grosse, W. Heise, and G. Gosztonyi, Spongiform encephalopathy in AIDS dementia complex: report of five cases., J. Acquir. Immune Defic. Syndromes 2:374–381 (1989).Google Scholar
  3. 3.
    B.A. Bennett, C.E. Hyde, J.R. Pecora, and J.E. Clodfelter, Long-term cocaine administration is not neurotoxic to cultured fetal mesencephalic dopamine neurons, Neurosci. Lett. 153:210–214 (1993).PubMedCrossRefGoogle Scholar
  4. 4.
    B.A. Bennett, C.E. Hyde, J.R. Pecora, and J.E. Clodfelter, Differing neurotoxic potencies of methamphetamine, mazindol, and cocaine in mesencephalic cultures, J. Neuropathol. 60:1444–1452 (1993).Google Scholar
  5. 5.
    D.J. Benos, B.H. Hahn, J.K. Bubien, S. Ghosh, N.A. Mashburn, M.A. Chaikin, G.M. Shaw, and E.N. Benveniste, Envelope glycoprotein gp120 of human immunodeficiency virus type 1 alters ion transport in astrocytes: implications for AIDS dementia complex, Proc. Natl Acad Sci. USA 91:494–498 (1994).PubMedCrossRefGoogle Scholar
  6. 6.
    L. Brenneman, G.L. Westbrook, S.P. Fitzgerald, D.L. Ennist, K.L. Elkins, M.R. Ruff, and C.B. Pert, Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide., Nature 335:639–642 (1988).PubMedCrossRefGoogle Scholar
  7. 7.
    C. Cerruti, M. Drian, J. Kamenka, and A. Privat, Localization of dopamine carriers by BTCP, a dopamine uptake inhibitor, on nigral cells cultured in vitro., Brain Res. 555:346–355 (1991).CrossRefGoogle Scholar
  8. 8.
    A. Ciardo and J. Meldolesi, Effects of the HIV-1 envelope glycoprotein gp120 in cerebellar cultures. [Ca2+]i increases in a glial cell subpopulation., Euro. J. Neurosci. 5:1711–1718 (1993).CrossRefGoogle Scholar
  9. 9.
    V.L. Dawson, T.M. Dawson, GR. Uhl, and S.H. Snyder, Human immunodefiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures, Proc. Natl. Acad. Sci. USA 90:3256–3259 (1993).PubMedCrossRefGoogle Scholar
  10. 10.
    E.B. Dreyer, P.K. Kaiser, J.T. Offerman, and S.A. Lipton, HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists., Science 248:364–367 (1990).PubMedCrossRefGoogle Scholar
  11. 11.
    D.H. Gabuzda, D.D. Ho, S.M. de la Monte, M.S. Hirsch, T.R. Rota, and R.A. Sobel, imunohistochemical identification of HTLV-III antigen in brains of patients with AIDS., Ann. Neurol 20:289–295 (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    D.H. Gabzuda and M.S. Hirsch, Neurologic manifestations of infection with human immunodeficiency virus., Ann. Int. Med. 107:383–391 (1987).CrossRefGoogle Scholar
  13. 13.
    D. Giulian, E. Wendt, K. Vaca, and C.A. Noonan, The envelope glycoprotein of human immunodeficiency virus type-1 stimulates release of neurotoxins from monocytes., Proc. Natl. Acad. Sci. USA 90:2769–2773 (1993).PubMedCrossRefGoogle Scholar
  14. 14.
    D. Giulian, K. Vaca, and C.A. Noonan, Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1., Science 250:1593–1596 (1990).PubMedCrossRefGoogle Scholar
  15. 15.
    M.-L. Gougeon and L. Montagnier, Apoptosis in AIDS, Science 260:1269–1270 (1993).PubMedCrossRefGoogle Scholar
  16. 16.
    H. Groux, G. Torpier, D. Monte, Y. Mouton, A. Capron, and J.C. Ameisen, Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals, J. Exp. Med. 175:331–340 (1992).PubMedCrossRefGoogle Scholar
  17. 17.
    N.L. Haigwood, C.B. Barker, K.W. Higgins, P.V. Skiles, G.K. Moore, K.A. Mann, D.R. Lee, J.W. Eichberg, and K.S. Steimer, Evidence for Neutralizing Antibodies Directed Against Conformational Epitopes of HIV-1 gp120., in: “Vaccines90”, Cold Spring Harbor Laboratories, New York, pp. 313–320 (1990).Google Scholar
  18. 18.
    K.D. Kieburtz, L.G. Epstein, H.A. Gelbard, and J.T. Greenamyre, Excitotoxicity and dopaminergic dysfunction in the acquired immunodeficiency syndrome dementia complex: therapeutic implications, Arch Neurol 48:1281–1284 (1991).PubMedCrossRefGoogle Scholar
  19. 19.
    S. Koenig, H.E. Gendelman, J.M. Orenstein, M.C. Dal Canto, G.H. Pezeshkpour, M. Yungbluth, F. Janotta, A. Aksamit, M.A. Martin, and A.S. Fauci, Detection of AIDS virus in macrophages in brain tissue from ADDS patients with encephalopathy., Science 233:1089–1093 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    J.A. Levy, A.D. Hoffman, S.M. Kramer, J.M. Shimabukuro, and L.S. Oshiro, Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS., Science 225:840–842 (1984).PubMedCrossRefGoogle Scholar
  21. 21.
    S.A. Lipton, Models of neuronal injury in AIDS: another role for the NMD A receptor?, Trends Neurosci. 15:75–79 (1992).PubMedCrossRefGoogle Scholar
  22. 22.
    S.A. Lipton, N.J. Sucher, P.K. Kaiser, and E.B. Dreyer, Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity., Neuron 7:111–118 (1991).PubMedCrossRefGoogle Scholar
  23. 23.
    T.M. Lo, C.J. Fallert, T.M. Piser, and S.A. Thayer, HIV-1 envelope protein evokes intracellular calcium oscillations in rat hippocampal neurons., Brain Res. 594:189–196 (1992).PubMedCrossRefGoogle Scholar
  24. 24.
    E. Masliah, N. Ge, M. Morey, R. DeTeresa, R.D. Terry, and C.A. Wiley, Cortical dendritic pathology in human immunideficiency virus encephalitis, Lab. Invest. 66:285–291 (1992).PubMedGoogle Scholar
  25. 25.
    E. Masliah, R.D. Terry, R.M. DeTeresa, and LA. Hansen, Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer’s disease, Neurosci. Lett. 103:234–239 (1989).PubMedCrossRefGoogle Scholar
  26. 26.
    W.E.G. Muller, H.C. Schroder, H. Ushijima, J. Dapper, and J. Bormann, gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine, Eur. J. Pharmacol. 226:209–214 (1992).PubMedCrossRefGoogle Scholar
  27. 27.
    B.A. Navia, B.D. Jordan, and R.W. Price, The AIDS dementia complex. I. Clinical features, Ann. Neurol 19:517–524 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    S. Patt, H.J. Gertz, L. Gerhard, and J. Cervos-Navarro, Pathological changes in dendrites of substantia nigra neurons in Parkinson’s disease: a Golgi study, Histol. Histopathol 6:373–380 (1991).PubMedGoogle Scholar
  29. 29.
    S. Perovic, C. Schleger, G. Pergande, S. Iskric, H. Ushijima, P. Rytik, and W.E.G. Muller, The triaminopyridine flupirtine prevents cell death in rat cortical cells induced by N-methyl-D-aspartate and gp120 of HIV-1, Eur. J. Pharmacol in press:(1995).Google Scholar
  30. 30.
    S.W. Perry, Organic mental disorders caused by HIV: update on early diagnosis and treatment, Am J. Psychiatry 147:696–710 (1990).PubMedGoogle Scholar
  31. 31.
    R.J. Pomerantz, D.R. Kuritzkes, S.M. DeLaMonte, T.R. Rota, A.S. Baker, D. Albert, D.H. Bor, E.L. Feldman, R.T. Schooley, and M.S. Hirsch, Infection of the retina by human immunodeficiency virus type I., New England J. Med. 317:1643–1647 (1987).CrossRefGoogle Scholar
  32. 32.
    R.W. Price, B. Brew, J. Sidtis, M. Rosenblum, A.C. Scheck, and P. Cleary, The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex, Science 239:586–592 (1988).PubMedCrossRefGoogle Scholar
  33. 33.
    R. Sanchez-Pescador, M.D. Power, P.J. Barr, K.S. Steimer, M.M. Stempien, S.L. Brown-Shimer, W.W. Gee, A. Renard, A. Randolph, J.A. Levy, D. Dina, and P.A. Luciw, Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2)., Science 227:484–492 (1985).PubMedCrossRefGoogle Scholar
  34. 34.
    T. Savio and G. Levi, Neurotoxicity of HIV coat protein gp120, NMDA receptors, and protein kinase C: a study with rat cerebellar granule cells cultures., J. Neurosci. Res. 34:265–272 (1993).PubMedCrossRefGoogle Scholar
  35. 35.
    C.J. Scandella, J. Kilpatrick, W. Lidster, C. Parker, J.P. Moore, G.K. Moore, K.A. Mann, P. Brown, S. Coates, B. Chapman, F.R. Masiarz, and K.S. Steimer, Nonaffinity purification of recombinant gp120 for use in AIDS vaccine development., AIDS Res. Hum. Retroviruses 9:1233–1244 (1993).PubMedCrossRefGoogle Scholar
  36. 36.
    K.S. Steimer, G.A. Van Nest, N.L. Haigwood, E.M. Tillson, C. George-Nascimento, P.J. Barr, and D. Dina, Recombinant env and gag Polypeptides in Characterizing HIV-1 Neutralizing Antibidies., in: “Vaccines 88”, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, pp. 347–355 (1988).Google Scholar
  37. 37.
    B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B.J. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Specific tropism of HIV-1 for microglial cells in primary human brain cultures, Science 249:549–553 (1990).PubMedCrossRefGoogle Scholar
  38. 38.
    G.T. Williams, Programmed cell death: apoptosis and oncogenesis, Cell 65:1097–1098 (1991).PubMedCrossRefGoogle Scholar
  39. 39.
    D.J. Wolff, G.A. Datto, R.A. Smatovicz, and R.A Tempsick, Identification and characterization of a calmodulin-dependent nitric oxide synthase from GH3 pituitary cells, J. Biol Chem. 268:9425–9429 (1993).PubMedGoogle Scholar
  40. 40.
    S.S. Zhan, K. Beyreuther, and H.P. Schmitt, Synaptophysin immunoreactivity of the cortical neuropil in vascular dementia of Binzwanger type compared with the dementia of Alzheimer type and nondemented controls, Dementia 5:79–87 (1994).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Barbara A. Bennett
    • 1
  • Daniel E. Rusyniak
    • 1
  • Charlotte K. Hollingsworth
    • 1
  1. 1.Department of Physiology and PharmacologyBowman Gray School of MedicineWinston-SalemUSA

Personalised recommendations