The Putative Role of HIV-1 Envelope Proteins in the Neuroimmunology and Neuropathology of CNS Aids

  • Prasad Koka
  • Jean E. Merrill


Cells of the immune and central nervous systems communicate or interact with each other through proinflammatory cytokines (Benveniste, 1994; Black, 1994; Williams et al., 1994). There also exist parallels between the immune and central nervous systems in human immunodeficiency virus type 1 (HIV-1)-mediated secondary effects possibly triggered among others by cytokines leading to pathological abnormalities. In the immune system, although the T-helper cells are affected by the direct infection with HIV-1, other subsets of cells or their function are also altered by the virus, despite the lack of infection of these other cell subsets by the virus. These include the CD8-positive suppressor T cells whose numbers are diminished and/or their cytotoxic function reduced indirectly by the virus (Ho et al., 1993; Watret et al., 1993). Similarly, the ability of B lymphoid cells to provide help to T cells is also affected, although HIV-1 does not productively infect B lymphoid cells (Maggi et al., 1994). Analogously, in the central nervous system (CNS), the blood-borne macrophages infected with the virus carry the virus across the blood-brain barrier to fuse with and infect microglial cells in the brain, and spread the infection to parenchymal microglial cells in vivo. While this gives rise to white matter pathology, the neurons in the gray matter of the CNS are not infected by the virus. But the damage done to oligodendrocytes and neurons is again indirect as for non-CD4 cells in the immune system and can occur even in the absence of viral infection of these cells and by interactions between viral envelope proteins and glial cells in the CNS.


Nitric Oxide Human Immunodeficiency Virus Vasoactive Intestinal Peptide Envelope Protein Human Immunodeficiency Virus Envelope 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Achim, C. L., Heyes, M. P., and Wiley, C. A., 1993, Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains, J. Clin. Invest. 91:2769–2775.PubMedCrossRefGoogle Scholar
  2. Atwood, W. J., Berger, J. R., Kaderman, R., Tornatore, C. S., and Major, E. O., 1993, Human immunodeficiency virus type 1 infection of the brain, Clin. Microbiol. Rev. 6:339–366.PubMedGoogle Scholar
  3. Atwood, W. J., Tornatore, C. S., Traub, R., Conant, K., Drew, P. D., and Major, E. O., 1994, Stimulation of HIV type 1 gene expression and induction of NF-kappaB (p50/p65)-binding activity in tumor necrosis factor alpha-treated human fetal glial cells, AIDS Res. Hum. Retrovir. 10:1207–1211.PubMedCrossRefGoogle Scholar
  4. Benveniste, E. N., 1994, Cytokine circuits in brain. Implications for AIDS dementia complex, in: HIV, AIDS, and the Brain, Volume 72, (R. W. Price and S. W. Perry, eds.) Raven Press, New York, pp. 71–88.Google Scholar
  5. Benos, D. J., Hahn, B. H., Bubien, J. K., Ghosh, S. K., Mashbarn, N. A., Chaikin, M. A., Shaw, G. M., and Benveniste, E. N., 1994, Envelope glycoprotein gp120 of human immunodeficiency virus type 1 alters ion transplant in astrocytes: Implications for AIDS demential complex, Proc. Natl. Acad. Sci. USA 91:494–498.PubMedCrossRefGoogle Scholar
  6. Bhat, S., Spitalmik, S. L., Gonzalez-Scarano, F., and Silberberg, D. H., 1991, Galactosylceramide or a derivative is an essential component of the neural receptor for human immunodeficiency virus type 1 envelope glycoprotein gp120, Proc. Natl. Acad. Sci. USA 88:7131–7136.PubMedCrossRefGoogle Scholar
  7. Black, P. H., 1994, Immune system-central nervous system interactions: Effect and immunomodulatory consequences of immune system mediators on the brain, Antimicrob. Agents Chemother. 38:7–12.PubMedCrossRefGoogle Scholar
  8. Blumberg, B. M., Gelbard, H. A., and Epstein, L. G., 1994, HIV-1 infection of the developing nervous system: Central role of astrocytes in pathogenesis, Virus Res. 32:253–267.PubMedCrossRefGoogle Scholar
  9. Boje, K. M., and Arora, P. K., 1992, Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death, Brain Res. 587:250–256.PubMedCrossRefGoogle Scholar
  10. Brenneman, D. E., Westbrook, G. L., Fitzgerald, S. P., Ernist, D. L., Elkins, K. L., Rudd, M. R., and Pert, C. B., 1988, Neuronal killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide, Nature 335:639–642.PubMedCrossRefGoogle Scholar
  11. Brenneman, D. E., McCune, S. K., Mervis, R. F., and Hill, J. M., 1994, gp120 as an etiologic agent for NeuroAIDS: Neurotoxicity and model systems, Adv. Neuroimmunol. 4:157–165.PubMedCrossRefGoogle Scholar
  12. Brosnan, C. F., Battistini, L., Raine, C. S., Dickson, D. W., Casadevall, A., and Lee, S. C., 1994, Reactive nitrogen intermediates in human neuropathology: An overview. Dev. Neurosci. 16:152–161.PubMedCrossRefGoogle Scholar
  13. Budka, H., 1989, Human immunodeficiency virus (HIV) induced disease of the central nervous system: Pathology and implications for pathogenesis, Acta Neuropathol. 77:225–236.PubMedCrossRefGoogle Scholar
  14. Budka, H., 1991, Neuropathology of human immunodeficiency virus infection, Brain Pathol. 1:163–180.PubMedCrossRefGoogle Scholar
  15. Bukrinsky, M. E., Nottet, H. S., Schmidtmayerova, H., Dubrovsky, L., Flanagan, C. R., Mullins, M. E., Lipton, S. A., and Gendelman, H. E., 1995, Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: Implications for HIV-associated neurological disease, J. Exp. Med. 181:735–745.PubMedCrossRefGoogle Scholar
  16. Campbell, I. L., Cutri, A., Wilkinson, D., Boyd, A. W., and Harrison, L. C., 1989, Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection, Proc. Natl. Acad. Sci. USA 86:4282–4286.PubMedCrossRefGoogle Scholar
  17. Campbell, I. L., Abraham, C. R., Mashih, E., Kemper, P., Inglis, J. D., Oldstone, M. B., and Mucke, L., 1993, Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6, Proc. Natl. Acad. Sci. USA 90:10061–10065.PubMedCrossRefGoogle Scholar
  18. Chao, C. C., Hu, S., Molitor, T. W., Shaskan, E. G., and Peterson, P. K., 1992, Neuroprotective role of IL-4 against activated microglia, J. Immunol. 149:2736–2741.PubMedGoogle Scholar
  19. Chao, C. C., Molitor, T. W., and Hu, S., 1993, Activated microglia mediate neuronal cell injury via a nitric oxide mechanism, J. Immunol. 151:1473–1481.PubMedGoogle Scholar
  20. Chelbi-Alix, M. K., Brouard, A., Boissard, C., Pelaprat, D., Rostene, W., and Thang, M. N., 1994, Induction by vasoactive intestinal peptide of interferon alpha/beta synthesis in glial cells but not in neurons, J. Cell. Physiol. 158:47–54.PubMedCrossRefGoogle Scholar
  21. Cowan, W. M., Fawcett, J. W., O’Leary, D. D. M., and Stanfield, B. B., 1984, Regressive events in neurogenesis, Science 225:1258–1265.PubMedCrossRefGoogle Scholar
  22. Cunha, F Q., Moncada, S., and Liew, F Y., 1992, Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-gamma in murine macrophages, Biochem. Biophys. Res. Commun. 182:1155–1159.PubMedCrossRefGoogle Scholar
  23. Dawson, T. M., Dawson, V. L., and Snyder, S. H., 1994, Molecular mechanisms of nitric oxide actions in the brain, Ann. N.Y. Acad. Sci. 738:76–85.PubMedCrossRefGoogle Scholar
  24. Dawson, V. L., Dawson, T. M., Uhl, G. R., and Snyder, S. H., 1993, Human immunodeficiency virus-1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures, Proc. Natl. Acad. Sci. USA 90:3256–3259.PubMedCrossRefGoogle Scholar
  25. de Cunha, A., Jefferson, J. J., Tyor, W. R., Glass, J. D., Jannotta, F. S., and Vitkovic, L., 1993, Control of astrocytosis by interleukin-1 and transforming growth factor-beta 1 in human brain, Brain Res. 631:39–45.PubMedCrossRefGoogle Scholar
  26. Dickson, D. W., Belman, A. L., and Park, Y. D., 1989, Central nervous system pathology in pediatric AIDS: An autopsy study, APMIS Suppl. 8:40.PubMedGoogle Scholar
  27. Dighiero, P., Reux, I., Hauw, J.-J., Fillet, A.-M., Courtois, Y., and Gourreau, O., 1994, Expression of nitric oxide synthase in cytomegalovirus infected cells of retinas from AIDS patients, Neurosci. Lett. 166:31–37.PubMedCrossRefGoogle Scholar
  28. Ding, A., Nathan, C. F., Graycar, J., Derynck, R., Stuehr, D. J., and Srimal, S., 1990, Macrophage deactivating factor and transforming growth factors-beta 1,-beta 2 and-beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma, J. Immunol. 145:940–947.PubMedGoogle Scholar
  29. Dreyer, E. B., Kaiser, P. K., Offermann, J. T., and Lipton, S.A., 1990, HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists, Science 248:364–367.PubMedCrossRefGoogle Scholar
  30. Dustin, M. L., Sirgen, K. H., Tuck, D. T., and Springer, T. A., 1988, Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1), J. Exp. Med. 167:1323–1340.PubMedCrossRefGoogle Scholar
  31. Earl, P. L., Koenig, S., and Moss, B., 1991, Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: Analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses, J. Virol. 65:31–41.PubMedGoogle Scholar
  32. Ehrenreich, H., Rieckmann, P., Sinowatz, F., Weih, K. A., Arthur, L. O., Goebel, F. D., Burd, P. R., Coligan, J. E., and Clouse, K. A., 1993, Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120, J. Immunol. 150:4601–4609.PubMedGoogle Scholar
  33. Elliott, M. J., Vadas, M. A., Cleland, L. G., Gamble, J. R., and Lopez, A. F., 1990, IL-3 and granulocyte-macrophage colony-stimulating factor stimulate two distinct phases of adhesion in human monocytes, J. Immunol. 145:167–176.PubMedGoogle Scholar
  34. Emilie, D., Peuchmaur, M., Maillot, M. C., Crevon, M. C., Brousse, N., Delfraissey, J. F., Dormont, J., and Galanaud, P., 1990, Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes, J. Clin. Invest. 86:148–159.PubMedCrossRefGoogle Scholar
  35. Epstein, L. G. and Gendelman, H. E., 1993, Human immunodeficiency virus type 1 infection of the nervous system: Pathogenetic mechanism, Ann. Neurol. 33:429–436.PubMedCrossRefGoogle Scholar
  36. Esiri, M. M., Morris, C. S., and Millard, P. R., 1991, Fate of oligodendrocytes in HIV-1 infection, AIDS 5:1081–1090.PubMedCrossRefGoogle Scholar
  37. Everall, I., Luthert, P., and Lantos, P., 1993, A review of neuronal damage in human immunodeficiency virus infection: Its assessment, possible mechanism and relationship to dementia, J. Neuropathol Exp. Neurol. 52:561–566.PubMedCrossRefGoogle Scholar
  38. Feuerstein, G. Z., Liu, T., and Barone, F. C., 1994, Cytokines, inflammation, and brain injury: Role of tumor necrosis factor-alpha, Cerebrovasc. Brain Metab. Rev. 6:341–360.PubMedGoogle Scholar
  39. Forstermann, U., Schmidt, H. H., Kohlhaas, K. L., and Murad, F., 1992, Induced RAW 264.7 macrophages express soluble and particulate nitric oxide synthase inhibition by transforming growth factor-beta, J. Pharmacol. 225:161–165.Google Scholar
  40. Frendl, G., and Beller, D. I., 1990, Regulation of macrophage activity by IL-3.1. IL-3 functions as a macrophage-activating factor with unique properties, inducing Ia and lymphocyte function-associated antigen-1 but not cytotoxicity, J. Immunol. 144:3392–3399.PubMedGoogle Scholar
  41. Gazzinelli, R. T., Oswald, I. P., James, S. L., and Sher, A., 1992, IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages, J. Immunol. 148:1792–1796.PubMedGoogle Scholar
  42. Gendelman, H. E., Genis, P., Jett, M., Zhai, Q. H., and Nottet, H. S., 1994, An experimental model system for HIV-1-induced brain injury, Adv. Neuroimmunol. 4:189–193.PubMedCrossRefGoogle Scholar
  43. Georgsson, G., 1994, Neuropathologic aspects of lentiviral infections, Ann. N.Y. Acad. Sci. 724:50–67.PubMedCrossRefGoogle Scholar
  44. Giulian, D., Vaca, K., and Noonan, C. A., 1990, Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1, Science 250:1593–1596.PubMedCrossRefGoogle Scholar
  45. Glass, J. D., Wesselingh, S. L., Seines, O. A., and McArthur, J. C., 1993, Clinical-neuropathologic correlation in HIV-associated dementia, Neurology 43:2230–2237.PubMedCrossRefGoogle Scholar
  46. Glowa, J. R., Panlilio, I. V., Brenneman, D. E., Gozer, I., Fridki, M., and Hill, J. M., 1992, Learning impairment following intracerebral administration of the HIV envelope protein gp120 on a VIP antagonist, Brain Res. 570:49–55.PubMedCrossRefGoogle Scholar
  47. Grau, G. E., Fajardo, L. F., Piguet, P. F., Lambert, P. H., and Vassalli, P., 1987, Tumor necrosis factor (cachetin) as an essential mediator in murine cerebral malaria, Science 237:1210–1212.PubMedCrossRefGoogle Scholar
  48. Gray, F., Belec, L., Keohane, C., DeTruchis, P., Clair, B., Durigon, M., Sobel, A., and Gherardi, R., 1994, Zidovudine therapy and HIV encephalitis: A 10-year neuropathological survey, AIDS 8:489–493.PubMedCrossRefGoogle Scholar
  49. Hatch, W. C., Pousada, E., Losev, L., Rashbaum, W. K., and Lyman, W. D., 1994, Neural cell targets of human immunodeficiency virus type 1 in human fetal organotypic cultures, AIDS Res. Hum. Retrovir. 10:1597–1607.PubMedCrossRefGoogle Scholar
  50. Hayman, M., Arbuthnott, G., Harkiss, G., Brace, H., Filippi, P., Philippon, V., Thomson, D., Vigne, R., and Wright, A., 1993, Neurotoxicity of peptide analogues of the transactivating protein tat from Maedi-Visna virus and human immunodeficiency virus, Neuroscience 53:1–6.PubMedCrossRefGoogle Scholar
  51. Hery, C., Sebire, G., Peudenier, S., and Tardieu, M., 1995, Adhesion to human neurons and astrocytes of monocytes: The role of interaction of CR3 and ICAM-1 and modulation by cytokines, J. Neuroimmunol. 57:101–109.PubMedCrossRefGoogle Scholar
  52. Hewett, S. J., and Choi, D. W., 1993, Cytokine-induced nitric oxide production by astroglia potentiates NMDA neurotoxicity in cortical cell cultures, Soc. Neurosci. Abstr. 19:25.Google Scholar
  53. Hewett, S. J., Corbett, J. A., McDaniel, M. L., and Choi, D. W., 1993, Interferon-gamma and interleukin-1 beta induce nitric oxide formation from primary mouse astrocytes, Neurosci. Lett. 164:229–232.PubMedCrossRefGoogle Scholar
  54. Hewett, S. J., Csernansky, C. A., and Choi, D. W., 1994, Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS, Neuron 13:487–494.PubMedCrossRefGoogle Scholar
  55. Heyes, M. P., Saito, K., and Markey, S. P., 1992, Human macrophages convert L-tryptophan to the neurotoxin guinolinic acid, Biochem. J. 283:633–635.PubMedGoogle Scholar
  56. Hill, J. M., Mervis, R. F., Avidor, R., Moody, T. W., and Brenneman, D. E., 1993, HIV envelope protein-induced neuronal damage and retardation of behavioral development in rat neonates, Brain Res. 603:222–233.PubMedCrossRefGoogle Scholar
  57. Ho, H. N., Hultin, L. E., Mitsuyasn, R. T., Matud, J. L., Hausner, M. A., Bockstoce, D., Chou, C. C., O’Rouke, S., Taylor, J. M., and Giorgi, J. V., 1993, Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens, J. Immunol. 150:3070–3079.PubMedGoogle Scholar
  58. Hofman, F. M., von Harwehr, R. I., Dinarello, C. A., Mizel, S. B., Hinton, D., and Merrill, J. E., 1986, Immunoregulatory molecules and IL2 receptors identified in multiple sclerosis brain, J. Immunol. 136:3239–3245.PubMedGoogle Scholar
  59. Hofman, F. M., Hinton, D. R., Baemayr, J., Weil, M., and Merrill, J. E., 1991, Lymphokines and immunoregulatory molecules in subacute sclerosis panencephalitis, Clin. Immunol. Immunopathol. 58:331–342.PubMedCrossRefGoogle Scholar
  60. Hurwitz, A. A., Berman, J. W., and Lyman, W. D., 1994, The role of the blood-brain barrier in HIV infection of the central nervous system, Adv. Neuroimmunol. 4:249–256.PubMedCrossRefGoogle Scholar
  61. Hurwitz, A. A., Lyman, W. D., and Berman, J. W., 1995, Tumor necrosis factor alpha and transforming growth factor beta upregulate astrocyte expression of monocyte chemoattractant protein-1, J. Immunol. 57:193–198.Google Scholar
  62. Hussian, F. A., Coulie, P. G., and van Snick, J., 1989, Distinct roles of IL-1 and IL-6 in human T cell activation, J. Immunol. 143:2520–2524.Google Scholar
  63. Hwang, S. S., Boyl, T. J., Lyerly, H. K., and Cullen, B. R., 1992, Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1, Science 257:535–537.PubMedCrossRefGoogle Scholar
  64. Jurgensen, C. H., Huber, B. E., Zimmerman, T. P., and Wolberg, G., 1990, 3-Deazaadenosine inhibits leukocyte adhesion and ICAM-1 biosynthesis in tumor necrosis factor-stimulated human endothelial cells, J. Immunol. 144:653–661.PubMedGoogle Scholar
  65. Kang, C.-Y, Itaniharan, K., Posner, M. R., and Nara, P., 1993, Identification of a neutralizing epitope conformationally affected by the attachment of CD4 to gp120, J. Immunol. 151:449–457.PubMedGoogle Scholar
  66. Katsuki, H., Nakai, S., Hirai, Y., Akaji, K., Kiso, Y., and Satoh, M., 1990, Interleukin 1β inhibits long-term potentiation in the CA3 region of mouse hippocampal slices, Eur. J. Pharmacol. 181:323–326.PubMedCrossRefGoogle Scholar
  67. Kitamura, Y., Arima, T., Sato, T., Nakamura, J., and Nomura, Y., 1995, Inhibitory effects of pentamidine on N-methyl-D-aspartate (NMDA) receptor/channels in the rat brain, Biol. Pharm. Bull. 18:234–238.PubMedCrossRefGoogle Scholar
  68. Koka, P., He, K., Zack, J. A., Kitchen, S., Peacock, W., Fried, I., Tran, T., Yashar, S., and Merrill, J. E., 1995a, HIV-1 envelope proteins induce IL1, TNFα and nitric oxide in glial cultures derived from fetal, neonatal, and adult human brain, J. Exp. Med. 182:941–952.PubMedCrossRefGoogle Scholar
  69. Koka, P., He, K., Camerini, D., Tran, T., Yashar, S., and Merrill, J. E., 1995b, The mapping of HIV-1 gp160 epitopes required for interleukin-1 and tumor necrosis factor a production in glial cells, J. Neuroimmunol. 57:179–191.PubMedCrossRefGoogle Scholar
  70. Kure, K., Llena, J. F., Lyman, W. D., Sociro, R., Weidenheim, K. M., Hirano, A., and Dickson, D. W., 1991, Human immunodeficiency virus-1 infection of the nervous system: An autopsy study of 268 adult, pediatric, and fetal brains, Hum. Pathol. 22:700–707.PubMedCrossRefGoogle Scholar
  71. Kurihara, N., Bertolini, D., Suda, T., Akayama, Y., and Roodman, G. D., 1990, IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release, J. Immunol. 144:4226–4230.PubMedGoogle Scholar
  72. Lancaster, J. R., Jr., 1992, Nitric oxide in cells, Am. Sci. 80:248–259.Google Scholar
  73. Lee, S. C., Dickson, D. W., Liu, W., and Brosnan, C. R., 1993a, Induction of nitric oxide synthase activity in human astrocytes by interleukin-1α and interferon 7, J. Neuroimmunol. 46:19–24.PubMedCrossRefGoogle Scholar
  74. Lee, S. C., Hatch, W. C., Liu, W., Dress, X., Lyman, W. D., and Dickson, D. W., 1993b, Productive infection of human fetal microglia by HIV-1, Am. J. Pathol. 143:1032–1039.PubMedGoogle Scholar
  75. Lee, S. C., Liu, W., Dickson, D. W., Brosnan, C. R., and Berman, J. W., 1993c, Cytokine production by human fetal microglia and astrocytes, J. Immunol. 15:2659–2667.Google Scholar
  76. Lee, S. C., Liu, W., Brosnan, C. R., and Dickson, D. W., 1994, GM-CSP promotes proliferation of human fetal and adult microglia in primary cultures, Glia 12:309–318.PubMedCrossRefGoogle Scholar
  77. Levi, G., Patrizio, M., Bernardo, A., Petricci, T. C., and Agresti, C., 1993, Human immunodeficiency virus coat protein gp120 inhibits the beta-adrenergic regulation of astroglial and microglial functions, Proc. Natl. Acad. Sci. USA 90:1541–1545.PubMedCrossRefGoogle Scholar
  78. Levy, J. A., 1993, Pathogenesis of human immunodeficiency virus infection, Microbiol. Rev. 57:183–210.PubMedGoogle Scholar
  79. Lipton, S. A., 1992, Requirement for macrophages in neuronal injury induced by HIV envelope protein gp120, Neuroreport 3:913–915.PubMedCrossRefGoogle Scholar
  80. Lipton, S. A., 1994a, AIDS-related dementia and calcium homeostasis, Ann. NY. Acad. Sci. 747:205–224.PubMedCrossRefGoogle Scholar
  81. Lipton, S. A., 1994b, HIV-related neuronal injury. Potential therapeutic intervention with calcium channel antagonists and NMDA antagonists, Mol. Neurobiol. 8:181–196.PubMedCrossRefGoogle Scholar
  82. Lipton, S. A., 1994c, Neuronal injury associated with HIV-1 and potential treatment with calcium-channel and NMDA antagonists, Dev. Neurosci. 16:145–151.PubMedCrossRefGoogle Scholar
  83. Lipton, S. A., Sucher, N. J., Kaiser, P. K., and Dryer, E. B., 1991, Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity, Neuron 7:111–118.PubMedCrossRefGoogle Scholar
  84. McConnell, J. R., Swindells, S., Ong, C. S., Gmeiner, W. H., Chu, W. K., Brown, D. K., and Gendelman, H. E., 1994, Prospective utility of cerebral proton magnetic resonance spectroscopy in monitoring HIV infection and its associated neurological impairment, AIDS Res. Hum. Retrovir. 10:977–982.PubMedCrossRefGoogle Scholar
  85. McInnes, A., and Rennick, D. M., 1988, Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells, J. Exp. Med. 167:598–611.PubMedCrossRefGoogle Scholar
  86. Maggi, E., Gindizi, M. G., Biagidti, R., Annunziato, R., Manetti, R., Piccinni, M. P., Parronchi, P., Sampognaro, S., Giannarini, L., and Zuccati, G., 1994, Th2-like CD8+ T cells showing B cell helper function and reduced cytolytic activity in human immunodeficiency virus type 1 infection, J. Exp. Med. 180:489–495.PubMedCrossRefGoogle Scholar
  87. Martin, S., Maruta, K., Burkhart, V., Gillis, S., and Kolb, H., 1988, IL-1 and IPN-gamma increase vascular permeability, Immunology 74:301–311.Google Scholar
  88. Masliah, E., Ge, N., Achim, C. L., and Wiley, C. A., 1994, Cytokine receptor alterations during HIV infection in the human central nervous system, Brain Res. 663:1–6.PubMedCrossRefGoogle Scholar
  89. Merrill, J. E., 1992, Cytokines and retroviruses, Clin. Immunol. Immunopathol. 64:23–27.PubMedCrossRefGoogle Scholar
  90. Merrill, J. E., and Chen, I. S. Y., 1991, HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease, FASEB J. 5:2391–2397.PubMedGoogle Scholar
  91. Merrill, J. E., and Martinez-Maza, O., 1993, Cytokines in AIDS-associated nervous and immune system dysfunction, in: HIV, AIDS, and the Brain, Volume 17 (E. B. deSouza, ed.), Academic Press, New York, pp. 243–266.Google Scholar
  92. Merrill, J. E., Koyanagi, Y., and Chen, I. S. Y., 1989, Interleukin-1 and tumor necrosis factor a can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor, J. Virol. 63:4404–4408.PubMedGoogle Scholar
  93. Merrill, J. E., Koyanagi, Y., Zack, J., Thomas, L., Martin, P., and Chen, I. S. Y., 1992, Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1, J. Virol. 66:2217–2225.PubMedGoogle Scholar
  94. Merrill, J. E., Ignarro, L. J., Sherman, M. P., Melinek, J., and Lane, T. E., 1993, Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide, J. Immunol. 151:2132–2141.PubMedGoogle Scholar
  95. Milstien, S., Sakai, N., Brew, B. J., Krieger, C., Vickers, J. H., Saito, K., and Heyes, M. R., 1994, Cerebrospinal fluid nitrite/nitrate levels in neurologic diseases, J. Neurochem. 63:1178–1180.PubMedCrossRefGoogle Scholar
  96. Mollace, V., Colasanti, M., Persichini, T., Bagetta, G., Lauro, G. M., and Nistico, G., 1993, HIV gp120 glyco-protein stimulates the inducible isoform of NO synthase in human cultured astrocytoma cells, Biochem. Biophys. Res. Commun. 194:439–445.PubMedCrossRefGoogle Scholar
  97. Moore, J. P., Thali, M., Jameson, B. A., Vignaux, R., Lewis, G. K., Poon, S.-W., Charles, M., Fung, M. S., Sun, B., Durda, P. J., Akerblom, L., Wahren, B., Ditto, D., Sattentau, Q. J., and Sodroski, J., 1993, Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1. Probing the structure of the C4 and V4 domains and the interaction of the C5 domain with the V3 loop, J. Virol. 67:4785–4796.PubMedGoogle Scholar
  98. Moore, J. P., Sattentau, Q. J., Way, R., and Sodroski, J., 1994, Probing the structure of the human immunodeficiency virus surface glycoprotein gp120 with a panel of monoclonal antibodies, J. Virol. 68:469–475.PubMedGoogle Scholar
  99. Moses, A. V., and Nelson, J. A., 1994, HIV infection of human brain capillary endothelial cells—Implications for AIDS dementia, Adv. Neuroimmunol. 4:239–247.PubMedCrossRefGoogle Scholar
  100. Moses, A. V., Bloom, F. E., Pauza, C. D., and Nelson, J. A., 1993, Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CDR/galactosylceramide-independent mechanism, Proc. Natl. Acad. Sci. USA 90:10474–10478.PubMedCrossRefGoogle Scholar
  101. Murphy, S., Simmons, M. L., Aqulillo, L., Garcia, A., Feinstein, D. L., Galea, E., Reis, D. J., Minc-Golomb, D., and Schwartz, J. P., 1993, Synthesis of nitric oxide in CNS glial cells, Trends Neurosci. 16:323–328.PubMedCrossRefGoogle Scholar
  102. Naif, H., Ho-Shon, M., Chang, J., and Cunningham, A. L., 1994, Molecular mechanisms of IL-4 effect on HIV expression in promonocytic cell lines and primary human monocytes, J. Leuk. Biol. 56:335–339.Google Scholar
  103. Nakajima, K., Martinez-Maza, O., Hirano, T., Breen, E. C., Nishanian, P. G., Salazar-Gonzalez, J. F., Fahey, J. L., and Kishimoto, T., 1989, Induction of IL6 (B cell stimulatory factor-2/IFN-β) production by HIV, J. Immunol. 142:531–536.PubMedGoogle Scholar
  104. Perry, V. H., Lawson, L. J., and Reid, D. M., 1994, Biology of the mononuclear phagocyte system of the central nervous system and HIV infection, J. Leuk. Biol. 56:399–406.Google Scholar
  105. Peudenier, S., Itery, C., Montagnier, L., and Tardieu, M., 1993, Human microglial cells characterization in cerebral tissue and in primary culture and study of their susceptibility to HIV-1 infection, Ann. Neurol. 29:152–159.CrossRefGoogle Scholar
  106. Philippon, V., Vellutini, C., Gambarelli, D., Harkiss, G., Arbuthnott, G., Metzger, D., Roubin, R., and Filippi, P., 1994, The basic domain of the lentiviral Tat protein is responsible for damages in mouse brain: Involvement of cytokines, Virology 205:519–529.PubMedCrossRefGoogle Scholar
  107. Pietraforte, D., Tritarelli, E., Testa, U., and Minetti, M., 1994, Gp120 HIV envelope glycoprotein increases the production of nitric oxide in human monocyte derived macrophages, J. Leuk. Biol. 55:175–182.Google Scholar
  108. Poli, G., Bressler, P., Kinter, A., Duh, E., Timmer, W. C., Rabson, A., Justement, J. S., Stanley, S., and Fauci, A. S., 1990, Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor a by transcriptional and post-transcriptional mechanisms, J. Exp. Med. 172:151–160.PubMedCrossRefGoogle Scholar
  109. Poli, G., Pantaleo, G., and Fauci, A. S., 1993, Immunopathogenesis of human immunodeficiency virus infection, Clin. Infect. Dis. 17:S224–S229.PubMedCrossRefGoogle Scholar
  110. Portegies, P., deGans, J., Lange, J. M. A., Deux, M. M. A., Speelman, H., Bakker, M., Danner, S. A., and Goudsmit, J., 1989, Declining incidence of AIDS demential complex after induction of zidovudine treatment, Br. Med. J. 299:819–821.CrossRefGoogle Scholar
  111. Portegies, P., Algra, P. R., Hollak, C. E., Prins, J. M., Reiss, P., Valk, J., and Lange, J. M., 1991, Response to cytarabine in progressive multifocal leucoencephalopathy in AIDS, Lancet 337:680–681.PubMedCrossRefGoogle Scholar
  112. Power, C., and Johnson, R. T., 1995, HIV-1 associated dementia: Clinical features and pathogenesis, Can. J. Neurol. Sci. 22:92–100.PubMedGoogle Scholar
  113. Power, C., McArthur, J. C., Johnson, R. T., Griffin, D. E., Glass, J. D., Perrymay, S., and Chesebro, B., 1994, Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences, J. Virol. 68:4643–4649.PubMedGoogle Scholar
  114. Price, R.N., Brew, B., Sidtis, J., Rosenblum, U., Scheck, A. C., and Cleary, P., 1988, The brain in AIDS: Central nervous system HIV-1 infection and AIDS demential complex, Science 939:586–592.CrossRefGoogle Scholar
  115. Pulliam, L., West, D., Haigwood, N., and Swanson, R. A., 1993, HIV-1 envelope gp120 alters astrocytes in human brain cultures, AIDS Res. Hum. Retrovir. 9:439–444.PubMedCrossRefGoogle Scholar
  116. Pulliam, L., Clarke, J. A., McGuire, D., and McGrath, M. S., 1994, Investigation of HIV-infected macrophage neurotoxin production from patients with AIDS dementia, Adv. Neuroimmunol. 4:195–198.PubMedCrossRefGoogle Scholar
  117. Raff, M. C., 1992, Social controls on cell survival and cell death, Nature 356:397–400.PubMedCrossRefGoogle Scholar
  118. Rousset, F., Billaud, M., Blanchard, D., Figdor, C., Lenois, G. M., Spits, H., and De Vries, J. E., 1989, IL-4 induces LFA-1 and LFA-3 expression on Burkitt’s lymphoma cell lines. Requirement of additional activation by phorbol myristate acetate for induction of homotypic cell adhesions, J. Immunol. 143:1490–1498.PubMedGoogle Scholar
  119. Schneider-Schaulies, J., Schneider-Schaulies, S., Brinkmann, R., Tas, P., Halbrugge, M., Walter, V., Holmes, H. C., and terMeulen, V., 1992, HIV-1 gp120 receptor on CD4 negative brain cells activates a tyrosine kinase, Virology 191:765–772.PubMedCrossRefGoogle Scholar
  120. Sharer, L. R., Dowling, P. C., Michaels, J., Cook, J. D., Menonna, J., Blumberg, B. M., and Epstein, L. G., 1990, Spinal cord disease in children with HIV-1 infection: A combined molecular biological and neuropathological study, Neuropathol. Appl. Neurobiol. 16:317–327.PubMedCrossRefGoogle Scholar
  121. Sharpless, N., Gilbert, D., Vandercam, B., Zhou, J. M., Verdin, E., Ronnett, G., Friedman, E., and Dubois-Dalcq, M., 1992, The restricted nature of HIV-1 tropism for cultured neural cells, Virology 191:813–825.PubMedCrossRefGoogle Scholar
  122. Simmons, M. L., and Murphy, S., 1993, Cytokines regulate L-arginine-dependent cyclic GMP production in rat glial cells, Eur. J. Neurosci. 5:825–831.PubMedCrossRefGoogle Scholar
  123. Soliven, B., and Albert, J., 1992, Tumor necrosis factor modulates Ca2+ currents in cultured sympathetic neurons, J. Neurosci. 12:2665–2671.PubMedGoogle Scholar
  124. Sundar, S. K., Cierpical, M. A., Kamaraju, L. S., Long, S., Hsieh, S., Lorenz, C., Aaron, M., Richie, J. C., and Weiss, J. M., 1991, Human immunodeficiency virus glycoprotein (gp120) infused into rat brain induced interleukin 1 to elevate pituitary adrenal activity and decrease peripheral cellular immune responses, Proc. Nail Acad. Sci. USA 88:11246–11250.CrossRefGoogle Scholar
  125. Syndulko, K., Singer, E. J., Nogales-Gaete, J., Conrad, A., Schmid, P., and Tourtellotte, W. W., 1994, Laboratory evaluations in HIV-1-associated cognitive/motor complex, Psychiatr. Clin. North Am. 17:91–123.PubMedGoogle Scholar
  126. Talley, A. K., Dewhurst, S., Perry, S. W., Dollard, S. C., Gummuluru, S., Fine, S. M., New, D., Epstein, L. G., Gendelman, H. E., and Gelbard, H. A., 1995, Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: Protected by the antioxidant N-acetylcysteine and the genes bc1-2 and crmA, Mol. Cell. Biol. 15:2359–2366.PubMedGoogle Scholar
  127. Tardieu, M., and Janabi, N., 1994, HIV-1 and the developing human nervous system: In vivo and in vitro aspects, Dev. Neurosci. 16:137–144.PubMedCrossRefGoogle Scholar
  128. Tardieu, M., Mayaux, M.J., Seibel, N., Funck-Brentano, I., Straub, E., Teglas, J. P., and Blanche, S., 1995, Cognitive assessment of school-age children infected with maternally transmitted human immunodeficiency virus type 1, J. Pediatr. 126:375–379.PubMedCrossRefGoogle Scholar
  129. Thornhill, M. H., Kyan-Aung, U., and Haskard, D. O., 1990, IL-4 increases human endothelial cell adhesiveness for T cells but not for neutrophils, J. Immunol 144:3060–3065.PubMedGoogle Scholar
  130. Toggas, S. M., Mashiah, E., Rockenstein, E. M., Rail, G. F., Abraham, C. R., and Mucke, L., 1994, Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice, Nature 367:188–193.PubMedCrossRefGoogle Scholar
  131. Tornatore, C., Myers, K., Atwood, W., Conant, K., and Major, E., 1994a, Temporal patterns of human immunodeficiency virus type 1 transcripts in human fetal astrocytes, J. Virol. 68:93–102.PubMedGoogle Scholar
  132. Tornatore, C., Chandra, R., Berger, J. R., and Major, E. O., 1994b, HIV-1 infection of subcortical astrocytes in the pediatric central nervous system, Neurobiology 44:481–487.Google Scholar
  133. Tyor, W. R., Glass, J.-D., Griffin, J. W., Becker, P. S., McArthur, J. C., Begman, L., and Griffin, D. E., 1992, Cytokine expression in the brain during the acquired immunodeficiency syndrome, Ann. Neurol. 31:349–357.PubMedCrossRefGoogle Scholar
  134. Tyor, W. R., Power, C., Gendelman, H. E., and Markham, R. B., 1993a, A model of human immunodeficiency virus encephalitis in scid mice, Proc. Natl. Acad. Sci. USA 90:8658–8662.PubMedCrossRefGoogle Scholar
  135. Tyor, W. R., Glass, J. D., Baumrine, N. M., Arthur, J. C., Griffin, J. W., Becker, P. S., and Griffin, D. E., 1993b, Cytokine expression of macrophages in HIV-1 associated vacuolar myelopathy, Neurology 43:1002–1009.PubMedCrossRefGoogle Scholar
  136. Tyor, W. R., Wesselingh, S. L., Griffin, J. W., McArthur, J. C., and Griffin, D. E., 1995, Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy, J. Acq. Immune Defic. Syndr. 9:379–388.Google Scholar
  137. Valentin, A., Lundin, K., Patarroyo, M., and Asjo, B., 1990, The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells, J. Immunol. 144:934–937.PubMedGoogle Scholar
  138. Valone, F. H., and Epstein, L. B., 1988, Biphasic platelet-activating factor synthesis by human monocytes stimulated with IL-1β, tumor necrosis factor, or IFN-γ, J. Immunol. 141:3945–3950.PubMedGoogle Scholar
  139. Vazeux, R., Lacroix-Gaudo, C., Blanche, S., Cumont, M.-C., Hemin, D., Gray, F., Boccon-Gibod, L., and Tardieu, M., 1992, Low levels of human immunodeficiency virus replication in the brain tissue of children with severe acquired immunodeficiency syndrome encephalopathy, Am. J. Pathol. 140:149–156.Google Scholar
  140. Vitkovic, L., de Cunha, A., and Tyor, W. R., 1994, Cytokine expression and pathogenesis in AIDS brain, in: HIV, AIDS, and the Brain, Volume 72, (R. W. Price and S. W. Perry, eds.) Raven Press, New York, pp. 203–222.Google Scholar
  141. Vitkovic, L., Stover, E., and Koslow, S. H., 1995, Animal models recapitulate aspects of HIV/CNS disease, AIDS Res. Hum. Retrovir. 11:753–759.PubMedCrossRefGoogle Scholar
  142. Wahl, L. M., Corcoran, M. L., Pyle, S. W., Arthur, L. O., Harel-Bellan, A., and Farrar, W. L., 1989, Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1, Proc. Natl. Acad. Sci. USA 86:621–625.PubMedCrossRefGoogle Scholar
  143. Wahl, S. M., Allen, J. B., McCartney-Francis, N., Morganti-Kossmann, M. C., Kossman, T., Ellingsworth, L., Moi, U. E. H., Mergennagen, S. E., and Orenstein, T. M., 1991, Macrophage and astrocyte derived transforming growth factor β, J. Exp. Med. 173:981–990.PubMedCrossRefGoogle Scholar
  144. Watkins, B. A., Dorn, H. H., Kelly, W. B., Armstrong, R. C., Potts, B. J., Michaels, F., Kutfta, C. V., and Dubois-Dalcq, M., 1990, Specific tropism of HIV-1 for microglial cells in primary human brain cultures, Science 249:549–554.PubMedCrossRefGoogle Scholar
  145. Watret, K. C., Whitetaw, J. A., Froebl, K. S., and Bird, A. G., 1993, Phenotypic characterization of CD8+ T cell populations in HIV disease and in anti-HIV immunity, Clin. Exp. Immunol. 92:93–99.PubMedCrossRefGoogle Scholar
  146. Weis, S. H., Haug, H., and Budka, H., 1993, Astroglial changes in the cerebral cortex of AIDS brains: A morphometric and immunohistochemical investigation, Neuropathol. Appl. Neurobiol. 19:329–342.PubMedCrossRefGoogle Scholar
  147. Wesselingh, S. L., Power, V., Glass, J. D., Tyor, W. R., McArthur, J. G., Farber, J.-M., Griffin, J. W., and Griffin, D.-E., 1993, Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia, Ann. Neurol. 33:576–583.PubMedCrossRefGoogle Scholar
  148. Wesselingh, S. L., Glass, J., McArthur, J. C., Griffin, J. W., and Griffin, D. E., 1994, Cytokine dysregulation in HIV-associated neurological disease, Adv. Neuroimmunol. 4:199–206.PubMedCrossRefGoogle Scholar
  149. Williams, K., Ulvestad, E., and Antel, J., 1994, Immune regulatory and effector properties of human adult microglia studies in vitro and in situ, Adv. Neuroimmunol. 4:273–281.PubMedCrossRefGoogle Scholar
  150. Wilt, S. G., Milward, E., Zhou, J. M., Nagasato, K., Patton, H., Rusten, R., Griffin, D. E., O’Connor, M., and Dubois-Dalcq, M., 1995, In vitro evidence for a dual role of tumor necrosis factor-alpha in human immunodeficiency virus type 1 encephalopathy, Ann. Neurol. 37:381–394.PubMedCrossRefGoogle Scholar
  151. Yeung, M. C., Pulliam, L., and Lau, A. S., 1995, The HIV envelope protein gp120 is toxic to human brain cell cultures through the induction of interleukin-6 and tumor necrosis factor-alpha, AIDS 9:137–143.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Prasad Koka
    • 1
  • Jean E. Merrill
    • 2
  1. 1.Division of Hematology-Oncology, Department of MedicineUniversity of CaliforniaLos AngelesUSA
  2. 2.Department of ImmunologyBerlex BiosciencesRichmondUSA

Personalised recommendations