Skip to main content
SpringerLink
Log in

AIDS dementia and HIV-1-induced neurotoxicity: Possible pathogenic associations and mechanisms

  • Review
  • Published:
Journal of Biomedical Science

Abstract

AIDS Dementia Complex (ADC) is a syndrome of cognitive, behavioral, and motor deficits resulting from HIV-1 infection within the brain. ADC is characterized by variable degrees of neuronal cell death and gliosis that likely result, at least, in part from release of metabolic products, cytokines, and viral proteins from infected macrophages, although a unifying explanation for the neurological dysfunction has yet to be established. Major unanswered questions include: (i) do neurologic symptoms result from neuronal cell death and/or dysfunction in surviving neurons?; (ii) are viral genomic sequences determinants of neurotoxicity?; (iii) is HIV infection of neurons and astrocytes relevant to pathogenesis?, and (iv) what circulating factors within the brain affect neuronal cell survival and function? This review addresses the association between HIV-1 replication within the brain, production of potential neurotoxins and possible mechanisms of induction of neurotoxicity and neuronal dysfunction contributing to the pathogenesis of ADC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Achim CL, Heyes MP, Wiley CA. Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains. J Clin Invest 91:2769–2775;1993.

    PubMed  Google Scholar 

  2. Adle-Biassette H, Levy Y, Colombel M, Poron F, Natchev S, Keohane C, Gray F. Neuronal apoptosis in HIV infection in adults. Neuropathol Appl Neurobiol 21:218–227;1995.

    PubMed  Google Scholar 

  3. Agy MB, Frumkin LR, Corey L, Coombs RW, Wolinsky SM, Koehler J, Morton WR, Katze MG. Infection ofMacaca nemestrina by human immunodeficiency virus type-1. Science 257:103–106;1992.

    PubMed  Google Scholar 

  4. Albright AV, Strizki J, Harouse JM, Lavi E, O'Connor M, Gonzalez-Scarano F. HIV-1 infection of cultured human adult oligodendrocytes. Virology 217:211–219;1996.

    Article  PubMed  Google Scholar 

  5. Apostolski S, McAlarney T, Quattrini A, Levison SW, Rosoklija G, Lugaressi A, Corbo M, Sadiq SA, Lederman S, Hays AP, Latov N. The gp120 glycoprotein of human immunodeficiency virus type 1 binds to sensory ganglion neurons. Ann Neurol 34:855–863;1993.

    Article  PubMed  Google Scholar 

  6. Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG. Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci 14:5559–5569;1994.

    PubMed  Google Scholar 

  7. Atwood WJ, Berger JR, Kaderman R, Tornatore CS, Major EO. Human immunodeficiency virus type 1 infection of the brain. Clin Microbiol Rev 6:339–366;1993.

    PubMed  Google Scholar 

  8. Aylward EH, Brettschneider PD, McArthur JC, Harris GJ, Schlaepfer TE, Henderer JD, Barta PE. Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia. Am J Psychiatry 152:987–994;1995.

    PubMed  Google Scholar 

  9. Bagasra O, Lavi E, Bobroski L, Khalili K, Pestaner JP, Pomerantz RJ. Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: Identification by the combination of in situ PCR and immunohistochemistry. AIDS 10:573–578;1996.

    PubMed  Google Scholar 

  10. Barbour B, Szatkowski M, Ingledew N, Attwell D. Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells. Nature 342:918–920;1989.

    Article  PubMed  Google Scholar 

  11. Barillari G, Gendelman R, Gallo RC, Ensoli B. The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. Proc Natl Acad Sci USA 90:7941–7945;1993.

    PubMed  Google Scholar 

  12. Barks JDE, Sun R, Malinak C, Silverstein FS. gp120, an HIV-1 protein, increases susceptibility to hypoglycemic and ischemic brain injury in perinatal rats. Exp Neurol 132:123–133;1995.

    Article  PubMed  Google Scholar 

  13. Bennett BA, Rusyniak DE, Hollingsworth CK. HIV-1 gp120-induced neurotoxicity to mid-brain dopamine cultures. Brain Res 705:168–176;1995.

    Article  PubMed  Google Scholar 

  14. Benos DJ, Hahn BH, Bubien JK, Ghosh SK, Mashburn NA, Chaikin MA, Shaw GM, Benveniste EN. 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.

    PubMed  Google Scholar 

  15. Benos DJ, McPherson S, Hahn BH, Chaikin MA, Benveniste EN. Cytokines and HIV envelope glycoprotein gp120 stimulate Na+/H+ exchange in astrocytes. J Biol Chem 269:13811–13816;1994.

    PubMed  Google Scholar 

  16. Benveniste EN. Cytokine circuits in brain. Implications for AIDS dementia complex. In: Price RW, Perry SW, eds. HIV, AIDS and the Brain. New York, Raven Press, 71–88;1994.

    Google Scholar 

  17. Bernton EW, Bryant HU, Decoster MA, Orenstein JM, Ribas JL, Meltzer MS, Gendelman HE. No direct neuronotoxicity by HIV-1 virions or culture fluids from HIV-1-infected T cells or monocytes. AIDS Res Hum Retroviruses 8:495–503;1992.

    PubMed  Google Scholar 

  18. Bhat S, Spitalnik SL, Gonzalez-Scarano F, Silberberg DH. Galactosyl ceramide or a derivative is an essential component of the neural receptor from human immunodeficiency virus type 1 envelope gp120. Proc Natl Acad Sci USA 88:7131–7134;1991.

    PubMed  Google Scholar 

  19. Blumberg BM, Epstein LG, Saito Y, Chen D, Sharer LR, Anand R. Human immunodeficiency virus type 1nef quasispecies in pathological tissue. J Virol 66:5256–5264;1992.

    PubMed  Google Scholar 

  20. Bo L, Dawson TM, Wesselingh S, Mork S, Choi S, Kong PA, Hanley D, Trapp BD. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 36:778–786;1994.

    Article  PubMed  Google Scholar 

  21. Brake DA, Debouck C, Biesecker G. Identification of an Arg-Gly-Asp (RGD) cell adhesion site in human immunodeficiency virus type 1 transactivation protein, Tat. J Cell Biol 111:1275–1281;1990.

    Article  PubMed  Google Scholar 

  22. Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, Snyder SH. Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron 7:615–624;1991.

    Article  PubMed  Google Scholar 

  23. Brenneman DE, Westbrook GL, Fitzgerald SP, Ennist DL, Elkins KL, Ruff MR, Pert CB. Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Nature 335:639–642;1988.

    Article  PubMed  Google Scholar 

  24. Brew BJ, Rosenblum M, Cronin K, Price RW. AIDS dementia complex and HIV-1 brain infection: Clinical-virological correlations. Ann Neurol 38:563–570;1995.

    Article  PubMed  Google Scholar 

  25. Brew BJ, Corbeil J, Pemberton L, Evans L, Saito K, Penny R, Cooper DA, Heyes MP. Quinolinic acid production is related to macrophage tropic isolates of HIV-1. J Neurovirol 1:369–374;1995.

    PubMed  Google Scholar 

  26. Brosnan CF, Battistini L, Raine CS, Dickson DW, Casadevall A, Lee SC. Reactive nitrogen intermediates in human neuropathology: An overview. Dev Neurosci 16:152–161;1994.

    PubMed  Google Scholar 

  27. Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L. Brain pathology induced by infection with the HIV: A histological, immunocytochemical, and EM study of 100 autopsy cases. Acta Neuropathol (Berl) 75:185–198;1987.

    Article  PubMed  Google Scholar 

  28. Budka H, Lassman H. Human immunodeficiency virus in glial cells? J Infect Dis 157:203;1988.

    PubMed  Google Scholar 

  29. Budka H. Neuropathology of human immunodeficiency virus infection. Brain Pathol 1:163–175;1991.

    PubMed  Google Scholar 

  30. Bukrinsky MI, Nottet HSLM, Schmidtmayerova H, Dubrovsky L, Flanagan CR, Mullins ME, Lipton SA, Gendelman HE. 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;1995.

    Article  PubMed  Google Scholar 

  31. Buonaguro L, Barillari G, Chang HK, Bohan CA, Kao V, Morgan R, Gallo RC, Ensoli B. Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. J Virol 66:7159–7167;1992.

    PubMed  Google Scholar 

  32. Buzy J, Brenneman DE, Pert CB, Martin A, Salazar A, Ruff MR. Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals blocked by peptide T. Brain Res 598:10–18;1992.

    Article  PubMed  Google Scholar 

  33. Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK. Activated microglia mediates neuronal cell injury via a nitric oxide mechanism. J Immunol 149:2735–2741;1992.

    Google Scholar 

  34. Chao CC, Hu S. Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cell cultures. Dev Neurosci 16:172–179;1994.

    PubMed  Google Scholar 

  35. Chaudhry FA, Lehre KP, van Lookeren Campagne M, Ottersen OP, Danbolt NC, Storm-Mathisen J. Glutamate transporters in glial plasma membranes: Highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 15:711–720;1995.

    Article  PubMed  Google Scholar 

  36. Cheng-Mayer C, Rutka JT, Rosenblum ML, McHugh T, Stites DP, Levy JA. Human immunodeficiency virus can productively infect cultured human glial cells. Proc Natl Acad Sci USA 84:3526–3530;1987.

    PubMed  Google Scholar 

  37. Cheng-Mayer C, Levy JA. Distinct biological and serological properties of human immunodeficiency virus from the brain. Ann Neurol 23 (suppl):S58-S61;1988.

    Article  PubMed  Google Scholar 

  38. Cheng-Mayer C, Weiss C, Seto D, Levy JA. Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. Proc Natl Acad Sci USA 86:8575–8579;1989.

    PubMed  Google Scholar 

  39. Chiodi F, Fuerstenberg S, Gidland M, Asjo B, Fenyo EM. Infection of brain-derived cells with the human immunodeficiency virus. J Virol 61:1244–1247;1987.

    PubMed  Google Scholar 

  40. Chiodi F, Keys B, Albert J, Hagberg L, Lundeberg J, Uhlén M, Fenyö EM, Norkrans G. Human immunodeficiency virus type 1 is present in the cerebrospinal fluid of a majority of infected individuals. J Clin Microbiol 30:1768–1771;1992.

    PubMed  Google Scholar 

  41. Ciardo A, Meldolesi J. Effects of the HIV-1 envelope glycoprotein gp120 in cerebellar cultures. [Ca2+]i increases in a glial cell subpopulation. Eur J Neurosci 5:1711–1718;1993.

    PubMed  Google Scholar 

  42. Clements JE, Anderson MG, Zink MC, Joag SV, Narayan, O. The SIV model of AIDS encephalopathy: Role of neurotropic viruses in diseases. In: Price RW, Perry SW, eds. HIV, AIDS and the Brain. New York, Raven Press, 147–157;1994.

    Google Scholar 

  43. Collman R, Godfrey B, Cutilli J, Rhodes A, Hassan NF, Sweet R, Douglas SD, Friedman H, Nathanson N, Gonzalez-Scarano F. Macrophage-tropic strains of human immunodeficiency virus type 1 utilize the CD4 receptor. J Virol 64:4468–4476;1990.

    PubMed  Google Scholar 

  44. Conant K, Ma M, Nath A, Major EO. Extracellular human immunodeficiency virus type 1 Tat protein is associated with an increase in both NF-kB binding and protein kinase C activity in primary human astrocytes. J Virol 70:1384–1389;1996.

    PubMed  Google Scholar 

  45. Corboy JR, Buzy JM, Zink C, Clements JE. Expression directed from HIV long terminal repeats in the central nervous system of transgenic mice. Science 258:1804–1808;1992.

    PubMed  Google Scholar 

  46. Cupp C, Taylor JP, Khalili K, Amini S. Evidence of stimulation of the transforming growth factor β1 promoter by HIV-1 Tat in cells derived from CNS. Oncogene 8:2231–2236;1993.

    PubMed  Google Scholar 

  47. Davis LE, Hjelle BL, Miller VE, Palmer DL, Llewellyn AL, Merlin TL, Young SA, Mills RG, Wachsman W, Wiley CA. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology 42:1736–1739;1992.

    PubMed  Google Scholar 

  48. Dawson TM, Dawson VL, Snyder SS. A novel neuronal messenger molecule in brain: The free radical, nitric oxide. Ann Neurol 32:297–311;1992.

    Article  PubMed  Google Scholar 

  49. Dawson VL, Dawson TM, London ED, Bredt DS, Snyder SH. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci USA 88:6368–6371;1991.

    PubMed  Google Scholar 

  50. Dawson VL, Dawson T, Uhl GR, Snyder SH. Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. Proc Natl Acad Sci USA 90:3256–3259;1993.

    PubMed  Google Scholar 

  51. Demuis A, Sebben M, Haynes L, Pin J-P, Bockaert J. NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336:68–70;1995.

    Google Scholar 

  52. Denis M. Tat protein from HIV-1 binds toMycobacterium avium via a bacterial integrin. J Immunol 153:2072–2081;1994.

    PubMed  Google Scholar 

  53. Di Stefano M, Wilt S, Gray F, Dubois-Dalcq M, Choidi F. HIV type 1 V3 sequences and the development of dementia during AIDS. AIDS Res Hum Retroviruses 12:471–476;1996.

    PubMed  Google Scholar 

  54. Dickson DW, Mattiace LA, Kure K, Hutchins K, Lyman WD, Brosnan CF. Microglia in human disease, with an emphasis on acquired immune deficiency syndrome. Lab Invest 64:135–156;1991.

    PubMed  Google Scholar 

  55. Dickson D, Lee SC, Mattiace LA, Yen S-HC, Brosnan C. Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia 7:75–83;1993.

    Article  PubMed  Google Scholar 

  56. Dickson DW, Lee SC, Hatch W, Mattiace LA, Brosnan CF, Lyman WD. Macrophages and microglia in HIV-related CNS neuropathology. In: Price RW, Perry SW, eds. HIV, AIDS and the Brain. New York, Raven Press, 99–118;1994.

    Google Scholar 

  57. Dickson DW, Lee SC. Microglia in HIV-related CNS neuropathology: An update. J Neuro-AIDS 1:57–84;1996.

    Article  Google Scholar 

  58. Diop AG, Lesort M, Esclaire F, Sindou P, Couratier P, Hugon J. Tetrodotoxin blocks HIV coat protein (gp120) toxicity in primary neuronal cultures. Neurosci Lett 165:187–190;1994.

    Article  PubMed  Google Scholar 

  59. Diop AG, Lesort M, Esclaire F, Dumas H, Hugon J. Calbindin D28K-containing neurons, and not HSP70-expressing neurons, are more resistant to HIV-1 envelope (gp120) toxicity in cortical cell cultures. J Neurosci Res 42:252–258;1995.

    Article  PubMed  Google Scholar 

  60. Dreyer EB, Kaiser PK, Offermann JT, Lipton SA. HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 248:364–367;1990.

    PubMed  Google Scholar 

  61. Dumuis A, Pin J-P, Oomagari K, Sebben M, Bockaert J. Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors. Nature 347:182–184;1995.

    Article  Google Scholar 

  62. Ensoli B, Barillari G, Salahuddin SZ, Gallo RC, Wong-Staal F. Tat protein of HIV-1 stimulates growth of cells derived form Kaposi's sarcoma lesions of AIDS patients. Nature 345:84–86;1990.

    Article  Google Scholar 

  63. Ensoli B, Buonaguro L, Barillari G, Fiorelli V, Gendelman R, Morgan RA, Wingfield P, Gallo RC. Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J Virol 67:277–287;1993.

    PubMed  Google Scholar 

  64. Everall I, Luthert P, Lantos P. 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;1993.

    PubMed  Google Scholar 

  65. Everall IP, Glass JD, McArthur J, Spargo E, Lantos P. Neuronal density in the superior frontal and temporal gyri does not correlate with the degree of human immunodeficiency virus-associated dementia. Acta Neuropathol 88:538–544;1994.

    PubMed  Google Scholar 

  66. Falangola MF, Hanly A, Galvao-Castro B, Petito CK. HIV infection of human choroid plexus: A possible mechanism of viral entry into the CNS. J Neuropathol Exp Neurol 54:497–503;1995.

    PubMed  Google Scholar 

  67. Falangola MF, Hanly A, Galvao-Castro B, Petito CK. HIV infection of human choroid plexus: A possible mechanism of viral entry into the CNS. J Neuropathol Exp Neurol 54:497–503;1995.

    PubMed  Google Scholar 

  68. Fawell S, Seery J, Daikh Y, Moore C, Chen LL, Pepinsky B, Barsoum J. Tat-mediated delivery of heterologous proteins into cells. Proc Natl Acad Sci USA 91:664–668;1994.

    PubMed  Google Scholar 

  69. Flott B, Seifert W. Characterization of glutamate uptake systems in astrocyte primary cultures from rat brain. Glia 4:293–304;1991.

    Article  PubMed  Google Scholar 

  70. Foster AC, Collins JF, Schwarcz R. On the excitotoxic properties of quinolinic acid, 2,3-piperdine dicarboxylic acids and structurally related compounds. Neuropharmacology 22:1331–1342;1983.

    Article  PubMed  Google Scholar 

  71. Frankel AD, Pabo CO. Cellular uptake of the Tat protein from human immunodeficiency virus. Cell 55:1189–1193;1988.

    Article  PubMed  Google Scholar 

  72. Frankel AD, Biancalana S, Hudson D. Activity of synthetic peptides from the Tat protein of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 86:7397–7401;1989.

    PubMed  Google Scholar 

  73. Frumkin LR, Patterson BK, Leverenz JB, Agy MB, Wolinsky SM, Morton WR, Corey L. Infection ofMacaca nemestrina brain with human immunodeficiency virus type 1. J Gen Virol 76:2647;1995.

    Google Scholar 

  74. Funke I, Hahn A, Peter Reiber E, Weiss E, Riethmüller G. The cellular receptor (CD4) of the human immunodeficiency virus is expressed on neurons and glial cells in human brain. J Exp Med 165:1230–1235;1987.

    Article  PubMed  Google Scholar 

  75. Gallo P, Frei K, Rordorf C, Lazdins J, Tavolato B, Fontana A. Human immunodeficiency virus type 1 (HIV) infection of the central nervous system: An evaluation of cytokines in cerebrospinal fluid. J Neuroimmunol 23:109–116;1989.

    Article  PubMed  Google Scholar 

  76. Gallo P, Piccinno MG, Krzalic L, Tavolato B. Tumor necrosis factor alpha (TNFα) and neurological diseases: Failure in detecting TNFα in the cerebrospinal fluid from patients with multiple sclerosis, AIDS dementia complex, and brain tumors. J Immunol 23:41–44;1989.

    Google Scholar 

  77. Garry RF, Koch G. Tat contains a sequence related to snake neurotoxins. AIDS 6:1541–1560;1992.

    PubMed  Google Scholar 

  78. Gelbard HA, Dzenko KA, DiLoreto D, Del Cerro C, Del Cerro M, Epstein LG. Neurotoxic effects of tumor necrosis factor alpha in primary human neuronal cultures are mediated by activation of the glutamate AMPA receptor subtype: Implications for AIDS neuropathogenesis. Dev Neurosci 15:417–422;1993.

    PubMed  Google Scholar 

  79. Gelbard HA, James HJ, Sharer LR, Perry SW, Saito Y, Kazee AM, Blumberg BM, Epstein LG. Apoptotic neurons in brains from paediatric patients with HIV-1 encephalitis and progressive encephalopathy. Neuropathol Appl Neurobiol 21:208–217;1995.

    PubMed  Google Scholar 

  80. Gelbard HA, Nottet HSLM, Swindells S, Jett M, Dzenko KA, Genis P, White R, Wang L, Choi Y-B, Zhang D, Lipton SA, Tourtellotte WW, Epstein LG, Gendelman HE. Platelet-activating factor: A candidate human immunodeficiency virus type 1-induced neurotoxin. J Virol 68:4628–4635;1994.

    PubMed  Google Scholar 

  81. Gendelman HE, Lipton SA, Tardieu M, Bukrinsky MI, Nottet HSLM. The neuropathogenesis of HIV-1 infection. J Leukoc Biol 56:389–398;1994.

    PubMed  Google Scholar 

  82. Genis P, Jett M, Bernton EW, Boyle T, Gelbard HA, Dzenko K, Keane RW, Resnick L, Mizrachi Y, Volsky DJ, Epstein LG, Gendelman HE. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophages-astroglia interactions: Implications for the neuropathogenesis of HIV disease. J Exp Med 176:1703–1718;1992.

    Article  PubMed  Google Scholar 

  83. Giulian D, Wendt E, Vaca K, Noonan CA. The envelope glycoprotein of human immunodeficiency virus type 1 stimulates release of neurotoxins from monocytes. Proc Natl Acad Sci USA 90:2769–2773;1993.

    PubMed  Google Scholar 

  84. Giulian D, Vaca K, Corpuz M. Brain glia release factors with opposing actions upon neuronal survival. J Neurosci 13:29–37;1993.

    PubMed  Google Scholar 

  85. Giulian D, Li J, Li X, Goerge J, Rutecki PA. The impact of microglia-derived cytokines upon gliosis in the CNS. Dev Neurosci 16:128–136;1994.

    PubMed  Google Scholar 

  86. Glass JD, Wesselingh SL, Selnes OA, McArthur JC. Clinical-neuropathological correlation in HIV-associated dementia. Neurology 43:2230–2237;1993.

    PubMed  Google Scholar 

  87. Goswami KK, Miller RF, Harrison MJ, Hamel DJ, Daniels RS, Tedder RS. Expression of HIV-1 in the cerebrospinal fluid detected by the polymerase chain reaction and its correlation with central nervous system disease. AIDS 5:797–803;1991.

    PubMed  Google Scholar 

  88. Grant I, Atkinson H, Hellelink JR, Kennedy CJ, Richan DD, Spector SA, McCutchan JA. Evidence for early central nervous system involvement in the acquired immunodeficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Ann Intern Med 107:828–836;1987.

    PubMed  Google Scholar 

  89. Gray F, Gherardi R, Keohane C, Favolini M, Sobel A, Poirier J. Pathology of the central nervous system in 40 cases of acquired immune deficiency syndrome (AIDS). Neuropathol Appl Neurobiol 14:365–380;1988.

    PubMed  Google Scholar 

  90. Griffin DE, Wesselingh SL, McArthur JC. Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia. Ann Neurol 35:592–597;1994.

    Article  PubMed  Google Scholar 

  91. Grimaldi LME, Martino GV, Franciotta DM, Brustia R, Castagna A, Pristera R. Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement. Ann Neurol 29:21–25;1991.

    Article  PubMed  Google Scholar 

  92. Grimaldi LME, Martino GV, Franciotta DM, Brustia R, Castagna A, Pristera R, Lazzarin A. Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement. Ann Neurol 29:21–25;1991.

    Article  PubMed  Google Scholar 

  93. Gyorkey F, Meinick JL, Sinkovics JG, Gyorkey P. Retrovirus resembling HTLV in macrophages of patients with AIDS. Lancet i:106;1985.

    Article  Google Scholar 

  94. Harouse JM, Wroblewska Z, Laughlin A, Hickey WF, Schönwetter BS, Gonzalez-Scarano F. Human choroid plexus cells can be latently infected with human immunodeficiency virus. Ann Neurol 25:406–411;1989.

    Article  PubMed  Google Scholar 

  95. Harouse JM, Kunsch C, Hartle HT, Laughlin MA, Hoxie JA, Wigdahl B, Gonzalez-Scarano F. CD4-independent infection of human neural cells by human immunodeficiency virus type 1. J Virol 63:2527–2533;1989.

    PubMed  Google Scholar 

  96. Harouse JM, Bhat S, Spitalnik SL, Laughlin M, Stefano K, Silberberg DH, Gonzalez-Scarano F. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science 253:320–323;1991.

    PubMed  Google Scholar 

  97. Harouse JM, Collman RG, Gonzalez-Scarano F. Human immunodeficiency virus type 1 infection of SK-N-MC cells: Domains of gp120 involved in entry into a CD4-negative, galactosyl ceramide/3′ sulfo-galactosyl ceramide-positive cell line. J Virol 69:7383–7390;1995.

    PubMed  Google Scholar 

  98. Hatch WC, Pousada E, Losev L, Rashbaum WK, Lyman WD. Neural cell targets of human immunodeficiency virus type 1 in human fetal organotypic cultures. AIDS Res Hum Retroviruses 10:1597–1607;1994.

    PubMed  Google Scholar 

  99. Hayman M, Arbuthnott G, Harkiss G, Brace H, Filippi P, Philippon V, Thomson D, Vigne R, Wright A. Neurotoxicity of peptide analogues of the transactivating protein Tat form Maedi-Visna virus and human immunodeficiency virus. Neuroscience 53:1–6;1993.

    Article  PubMed  Google Scholar 

  100. Heindel WC, Jernigan TL, Archibald SL, Achim CL, Masliah E, Wiley CA. The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection. Arch Virol 51:1129–1135;1194.

    Google Scholar 

  101. Helland DE, Welles JL, Caputo A, Haseltine WA. Transcellular transactivation by the human immunodeficiency virus type 1 Tat protein. J Virol 65:4547–4549;1991.

    PubMed  Google Scholar 

  102. Heyes MP, Rubinow D, Lane C, Markey SP. Cerebrospinal fluid quinolinic acid concentrations are increased in acquired immune deficiency syndrome. Ann Neurol 26:275–277;1989.

    Article  PubMed  Google Scholar 

  103. Heyes MP, Gravell M, London WT, Eckhaus M, Vickers JH, Yegey JA, April M, Blackmore D, Markey SP. Sustained increases in cerebrospinal fluid quinolinic acid concentrations in rhesus macques(Macaca mulatta) naturally infected with simian retrovirus type-D. Brain Res 531:148–158;1990.

    Article  PubMed  Google Scholar 

  104. Heyes MP, Lackner A. Increased cerebrospinal fluid quinolinic acid, kynurenic acid, andL-kynurenine in acute septicemia. J Neurochem 55:338–341;1990.

    PubMed  Google Scholar 

  105. Heyes MP, Brew BJ, Martin A, Price RW, Salazar AM, Sidtis JJ, Yergey JA, Mouradian M, Sadler AE, Keilp J, Rubinow D, Markey SP. Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: Relationship to clinical and neurological status. Ann Neurol 29:202–209;1991.

    Article  PubMed  Google Scholar 

  106. Heyes MP, Saito K, Markey SP. Human macrophages convertL-tryptophan into the neurotoxin quinolinic acid. Biochem J 283:633–635;1992.

    PubMed  Google Scholar 

  107. Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, Dilling LA, Elia J, Kruesi MJP, Lackner A, Larsen SA, Lee K, Leonard HL, Markey SP, Martin A, Milstein S, Mouradian MM, Pranzatelli MR, Quearry BJ, Salazar A, Smith M, Strauss SE, Sunderland T, Swedo SW, Tourtellotte WW. Quinolinic acid and kynurenine pathway metabolism in inflammatory and noninflammatory neurological disease. Brain 115:1249–1273;1992.

    PubMed  Google Scholar 

  108. Hirka G, Prakash K, Kawashima H, Plotkin SA, Andrews PW, Gonczol E. Differentiation of human embryonal carcinoma cells induces human immunodeficiency virus permissiveness which is stimulated by human cytomegalovirus coinfection. J Virol 65:2732–2735;1991.

    PubMed  Google Scholar 

  109. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123–126;1995.

    Article  PubMed  Google Scholar 

  110. Howcroft TK, Strebel K, Martin MA, Singer DS. Repression of MHC class I gene promoter activity by two-exon Tat of HIV. Science 260:1320–1322;1993.

    Google Scholar 

  111. Janssen RS, Cornblatz DR, Epstein LG, Foa RP, McArthur JC, Price RW. Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology 41:778–785;1991.

    PubMed  Google Scholar 

  112. Janssen RS, Nwanyanwu OC, Selik RM, Stehr-Green JK. Epidemiology of human immunodeficiency virus encephalopathy in the United States. Neurology 42:1472–1476;1992.

    PubMed  Google Scholar 

  113. Jessen KR, Morgan L, Brammer M, Mirsky R. Galactocerebroside is expressed by nonmyelin-forming Schwann cells in situ. J Cell Biol 101:1135–1143;1985.

    Article  PubMed  Google Scholar 

  114. Joag SV, Stephens EB, Galbreath D, Zhu GW, Li Z, Foresman L, Zhao L-J, Pinson DM, Narayan O. Simian immunodeficiency virus SIVmac chimeric virus whoseenv gene was derived from SIV-encephalitis brain is macrophage-tropic but not neurovirulent. J Virol 69:1367–1369;1995.

    PubMed  Google Scholar 

  115. Johnson RT, Glass JD, McArthur JC, Chesebro BW. Quantitation of human immunodeficiency virus in brains of demented and nondemented patients with acquired immunodeficiency syndrome. Ann Neurol 39:392–395;1996.

    Article  PubMed  Google Scholar 

  116. Jordan EK, Heyes MP. Virus isolation and quinolinic acid in primary and chronic similan immunodeficiency virus infection. AIDS 7:1173–1179;1993.

    PubMed  Google Scholar 

  117. Kahari V-M, Larjavi H, Uitto J. Differential regulation of extracellular matrix proteoglycan (PG) gene expression. J Biol Chem 266:10608–10615;1991.

    PubMed  Google Scholar 

  118. Kaiser PK, Offermann JT, Lipton SA. Neuronal injury due to HIV-1 envelope protein is blocked by anti-gp120 antibodies but not by anti-CD4 antibodies. Neurology 40:1757–1761;1990.

    PubMed  Google Scholar 

  119. Kanai Y, Hediger MA. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360:467–471;1992.

    Article  PubMed  Google Scholar 

  120. Kanai Y, Stelzner M, Nubberger S, Khawaja S, Hevert SC, Smith CP, Hediger MA. The neuronal and epithelial human high affinity glutamate transporter. J Biol Chem 269:20599–20606;1994.

    PubMed  Google Scholar 

  121. Kanai Y, Smith CP, Hediger MA. A new family of neurotransmitter transporters: The high-affinity glutamate transporters. FASEB J 8:1450–1459;1994.

    Google Scholar 

  122. Kato T, Hirano A, Llena JF, Dembitzer HM. Neuropathology of acquired immune deficiency syndrome (AIDS) in 53 autopsy cases with particular emphasis on microglial nodules and multinucleated giant cells. Acta Neuropathol 73:287–294;1987.

    Article  PubMed  Google Scholar 

  123. Kerr SJ, Armati PJ, Brew BJ. Neurocytotoxicity of quinolinic acid in human brain cultures. J Neurovirol 1:375–380;1995.

    PubMed  Google Scholar 

  124. Ketzler S, Weis S, Haug H, Budka H. Loss of neurons in the frontal cortex in AIDS brains. Acta Neuropathol Berl 80:92–94;1990.

    Article  PubMed  Google Scholar 

  125. Keys B, Albert J, Kovamees J, Chiodi F. Brain-derived cells can be infected with HIV isolates derived from both blood and brain. Virology 183:834–839;1991.

    Article  PubMed  Google Scholar 

  126. Kim SU, Moretto G, Lee V, Yu RK. Neuroimmunology of gangliosides in human neurons and glial cells in culture. J Neurosci Res 15:303–321;1986.

    Article  PubMed  Google Scholar 

  127. Kimura-Kuroda J, Nagashima K, Yasui K. Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture. Arch Virol 137:81–99;1994.

    Article  PubMed  Google Scholar 

  128. Koch C, Zador A. The function of dendritic spines: Devices subserving biochemical rather than electrical compartmentalization. J Neurosci 13:413–422;1993.

    PubMed  Google Scholar 

  129. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233:1089–1093;1986.

    Google Scholar 

  130. Kohleisen B, Neumann M, Herrmann R, Brack-Werner R, Krohn KJE, Ovod V, Ranki A, Erfle V. Cellular localization of Nef expressed in persistently HIV-1-infected low-producer astrocytes. AIDS 6:1427–1436;1993.

    Google Scholar 

  131. Kolson DL, Buchhalter J, Collman R, Hellmig B, Farrell CF, Debouck C, Gonzalez-Scarano F. HIV-1 Tat alters normal organization of neurons and astrocytes in primary rodent brain cell cultures: RGD sequence dependence. AIDS Res Hum Retroviruses 9:677–685;1993.

    PubMed  Google Scholar 

  132. Kolson DL, Collman R, Hrin R, Balliet JW, Laughlin M, McGann KA, Debouck C, Gonzalez-Scarano F. Human immunodeficiency virus type 1 Tat activity in human neuronal cells: Uptake and transactivation. J Gen Virol 75:1927–1934;1994.

    PubMed  Google Scholar 

  133. Kolson DL, Debouck C, Collman R, Gonzalez-Scarano F. Functional assay fortat, the transactivator protein of HIV-1. In: Adolph KW, ed. Methods in Molecular Genetics, Volume 4, Molecular Virology. San Diego, Academic Press, 69–75;1994.

    Google Scholar 

  134. Kondo K, Hashimoto H, Kitanaka J, Sawada M, Suzumura A, Marunouchi T, Baba A. Expression of glutamate transporters in cultured glial cells. Neurosci Lett 188;140–142;1995.

    Article  PubMed  Google Scholar 

  135. Korber BTM, Kunstman KJ, Patterson BK, Furtado M, McEvilly MM, Levy R, Wolinsky SM. Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: Evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences. J Virol 68:7467–7481;1994.

    PubMed  Google Scholar 

  136. Kovalchuk Y, Miller B, Sarantis M, Attwell D. Arachidonic acid depresses non-NMDA receptor currents. Brain Res 643:287–295;1994.

    PubMed  Google Scholar 

  137. Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV, Chen ISY. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 236:819–822;1987.

    PubMed  Google Scholar 

  138. Kriegler M, Perez C, DeFay K, Albert I, Lu SD. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: Ramifications for the complex physiology of TNF. Cell 53:45–53;1988.

    Article  PubMed  Google Scholar 

  139. Kuiken CL, Goudsmit J, Weiller GF, Armstrong JS, Hartman S, Porteigies P, Dekker J, Cornelissen M. Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex. J Gen Virol 76:175–180;1995.

    PubMed  Google Scholar 

  140. Kure K, Weidenheim KM, Lyman WD, Dickson DW. Morphology and distribution of HIV-1 gp41-positive microglia in subacute AIDS encephalitis. Acta Neuropathol 80:393–400;1990.

    Article  PubMed  Google Scholar 

  141. Kure K, Lyman WD, Weidenheim KM, Dickson DW. Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemical method. Am J Pathol 136:1085–1092;1990.

    PubMed  Google Scholar 

  142. Lafrenie RM, Wahl LM, Epstein JS, Hewlett IK, Yamada KM, Dhawan S. HIV-1-Tat modulates the function of monocytes and alters their interactions with microvessel endothelial cells. J Immunol 156:1638–1645;1996.

    PubMed  Google Scholar 

  143. Lane TE, Buchmeier MJ, Watry DD, Jakubowski DB, Fox HS. Serial passage of microglial SIV resulted in selection of homogeneous env quasispecies in the brain. Virology 212:458–465;1995.

    Article  PubMed  Google Scholar 

  144. Larrick JW, Wright SC. Cytotoxic mechanism of tumor necrosis factor-α. FASEB J 4:3215–3223;1990.

    PubMed  Google Scholar 

  145. Laurenzi MA, Siden A, Persson MAA, Norkrans G, Hagberg L, Chiodi F. Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system. Clin Immunol Immunopathol 57:233–241;1990.

    Article  PubMed  Google Scholar 

  146. Li CJ, Friedman DJ, Wang C, Metelev V, Pardee AB. Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. Science 268:429–431;1995.

    PubMed  Google Scholar 

  147. Li XL, Moudgil T, Vinters HV, Ho DD. CD4-independent, productive infection of a neuronal cell line by HIV type 1. J Virol 64:1383–1387;1990.

    PubMed  Google Scholar 

  148. Lipton SA, Sucher NJ, Kaiser PK, Dreyer EB. Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity. Neuron 7:111–118;1991.

    Article  PubMed  Google Scholar 

  149. Lipton SA. Memantine prevents HIV coat protein-induced neuronal injury in vivo. Neurology 42:1403–1405;1992.

    PubMed  Google Scholar 

  150. Llanes C, Collman RG, Hrin R, Kolson DL. Acetylcholinesterase expression in NTera 2 human neuronal cells: A model for developmental expression in the nervous system. J Neurosci Res 42:791–802;1995.

    Article  PubMed  Google Scholar 

  151. Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A. Human immunodeficiency virus type 1 Tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol 37:373–380;1995.

    Article  PubMed  Google Scholar 

  152. Mankowski JL, Spelman JP, Ressetar HG, Strndberg JD, Laterra J, Carter DL, Clements JE, Zink MC. Neurovirulent simian immunodeficiency virus replicates productively in endothelial cells of the central nervous system in vivo and in vitro. J Virol 68:8202–8208;1994.

    PubMed  Google Scholar 

  153. Mann DA, Frankel AD. Endocytosis and targeting of exogenous HIV-1 Tat protein. EMBO J 10:1733–1739;1991.

    PubMed  Google Scholar 

  154. Marcuzzi A, Weinberger J, Weinberger OK. Transcellular activation of the human immunodeficiency virus type 1 long terminal repeat in cocultured lymphocytes. J Virol 66:4228–4232;1992.

    PubMed  Google Scholar 

  155. Marcuzzi A, Lowy I, Weinberger OW. Transcellular activation of the human immunodeficiency virus type 1 long terminal repeat in T lymphocytes requires CD4-gp120 binding. J Virol 66:4536–4539;1992.

    PubMed  Google Scholar 

  156. Martin A, Heyes MP, Salazar AM, Kampen DL, Williams J, Law WA, Coats ME, Markey SP. Progressive slowing of reaction time and increasing cerebrospinal fluid concentrations of quinolinic acid in HIV-infected individuals. J Neuropsychiatry Clin Neurosci 4:270–279;1992.

    PubMed  Google Scholar 

  157. Martin RE, Bradsher RW. Fungal infections. In: Carlson RW, Geheb MA, eds. Principles and Practice of Medical Intensive Care. Philadelphia, Saunders, 444–448;1993.

    Google Scholar 

  158. Martinou J-C. Transforming growth factor β1 is a potent survival factor for rat embryo motoneurons in culture. Dev Brain Res 52:175–181;1990.

    Article  Google Scholar 

  159. Masliah E, Ge N, Achim CL, Hansen LA, Wiley CA. Selective neuronal vulnerability in HIV encephalitis. J Neuropathol Exp Neurol 51:585–593;1992.

    PubMed  Google Scholar 

  160. Masliah E, Achim CL, Ge N, DeTeresa R, Terry RD, Wiley CA. Spectrum of human immunodeficiency virus-associated neocortical damage. Ann Neurol 32:321–329;1992.

    Article  PubMed  Google Scholar 

  161. Masliah E, Ge N, Morey M, DeTeresa R, Terry RD, Wiley CA. Cortical dendritic pathology in human immunodeficiency virus encephalitis. Lab Invest 66:285–291;1992.

    PubMed  Google Scholar 

  162. Masliah E, Achim CL, Ge N, DeTeresa R, Wiley CA. Cellular neuropathology in HIV encephalitis. In: Price RW, Perry SW, eds. HIV, AIDS, and the Brain. New York, Raven Press, 119–131;1994.

    Google Scholar 

  163. Masliah E, Ge J, Achim CL, Wiley CA. Cytokine receptor alterations during HIV infection in the human central nervous system. Brain Res 663:1–6;1994.

    Article  PubMed  Google Scholar 

  164. Masliah E, Ge N, Achim CL, DeTeresa R, Wiley CA. Patterns of neurodegeneration in HIV encephalitis. J Neuro-AIDS 1:161–173;1996.

    Article  Google Scholar 

  165. McArthur JC. Neurologic manifestations of AIDS. Medicine 66:407–437;1987.

    PubMed  Google Scholar 

  166. McArthur JC, Selnes OA, Glass JD, Hoover DR, Bacellar H. HIV dementia: Incidence and risk factors. In: Price RW, Perry SW, eds. HIV, AIDS, and the Brain. New York, Raven Press, 251–272;1994.

    Google Scholar 

  167. Merrill JE, Koyanagi Y, Chen ISY. Interleukin-1 and tumor necrosis factor α can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. J Virol 63:4404–4408;1989.

    PubMed  Google Scholar 

  168. Merrill JE, Chen ISY. HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB J 5:2391–2397;1991.

    PubMed  Google Scholar 

  169. Miller B, Sarantis M, Traynelis SF, Attwell D. Potentiation of NMDA receptor currents by arachidonic acid. Nature 355:722–725;1992.

    Article  PubMed  Google Scholar 

  170. Mizrachi Y, Rodriguez I, Sweetnam PM, Rubinstein A, Volsky DJ. HIV type 1 infection of human cortical neuronal cells: Enhancement by select neuronal growth factors. AIDS Res Hum Retroviruses 10:1593–1596;1994.

    PubMed  Google Scholar 

  171. Molina J-M, Schindler R, Ferriani R, Sakaguchi M, Vannier E, Dinarello CA, Groopman JE. Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1). J Infect Dis 161:888–893;1990.

    PubMed  Google Scholar 

  172. Mollace V, Colasanti M, Persichini T, Bagetta G, Lauro GM, Nistico G. HIV gp120 glycoprotein stimulates the inducible isoform of NO synthase in human cultured astrocytoma cells. Biochem Biophys Res Commun 194:439–445;1993.

    Article  PubMed  Google Scholar 

  173. Mollace V, Colasanti M, Rodino P, Lauro GM, Nistico G. HIV coating gp 120 glycoprotein-dependent prostaglandin E2 release by human cultured astrocytoma cells is regulated by nitric oxide formation. Biochem Biophys Res Commun 203:87–92;1994.

    Article  PubMed  Google Scholar 

  174. Monken CE, Wu B, Srinivasan A. High resolution analysis of HIV-1 quasispecies in the brain. AIDS 9:345–349;1995.

    PubMed  Google Scholar 

  175. Moses HL, Yang EY, Pietenpol JA. TGF-β stimulation and inhibition of cell proliferation: New mechanistic insights. Cell 63:245–247;1990.

    Article  PubMed  Google Scholar 

  176. Moses AV, Stenglein SG, Nelson JA. HIV infection of the brain microvasculature and its contribution to the AIDS dementia complex. J Neuro-AIDS 1:85–100;1996.

    Article  Google Scholar 

  177. Murray EA, Rausch DM, Lendvay J, Sharer LR, Eiden LE. Cognitive and motor impairments associated with SIV infection in rhesus monkeys. Science 255:1246–1249;1992.

    PubMed  Google Scholar 

  178. Naichen Y, Martin J-L, Stella N, Magistretti PJ. Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes. Proc Natl Acad Sci USA 90:4042–4046;1993.

    PubMed  Google Scholar 

  179. Navia BA, Jordan BD, Price RW. The AIDS dementia complex. I. Clinical features. Ann Neurol 19:517–524;1986.

    Article  PubMed  Google Scholar 

  180. Navia B, Cho E-S, Petito C, Price RW. The AIDS dementia complex. II. Neuropathology. Ann Neurol 19:525–535;1986.

    Article  PubMed  Google Scholar 

  181. Nath A, Psocy K, Martin C, Knudsen B, Magnuson DSK, Haughey N, Geiger JD. Identification of a human immunodeficiency virus type 1 Tat epitope that is neuroexcitatory and neurotoxic. J Virol 70:1475–1480;1986.

    Google Scholar 

  182. Nathanson N, Cook DG, Kolson DL, Gonzalez-Scarano F. Pathogenesis of HIV encephalopathy. Ann NY Acad Sci 724:87–106;1994.

    PubMed  Google Scholar 

  183. Neumann M, Felber BK, Kleinschmidt A, Froese B, Erfle V, Pavlakis GN, Brack-Werner R. Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function. J Virol 69:2159–2167;1995.

    PubMed  Google Scholar 

  184. Niikura M, Dornadula G, Zhang H, Mukhtar M, Lingxun D, Khalili K, Bagasra O, Pomerantz RJ. Mechanisms of transcriptional activation and restriction of human immunodeficiency virus type 1 replication in an astrocytic glial cell. Oncogene (in press).

  185. Nishiyama M, Watanabe T, Ueda N, Tsukamoto H, Watanabe K. Arachidonate 12-lipoxygenase is localized in neurons, glial cells, and endothelial cells of the canine brain. J Histochem Cytochem 41:111–117;1993.

    PubMed  Google Scholar 

  186. Nokta MA, Hassan Ml, Loesch KA, Pollard RB. HIV-induced TNF-α regulates arachidonic acid and PGE2 release from HIV-infected mononuclear phagocytes. Virology 208:590–600;1995.

    Article  PubMed  Google Scholar 

  187. Nottet HSLM, Jett M, Flanagan CR, Zhai Q-H, Persidsky Y, Rizzino A, Bernton EW, Genis P, Baldwin T, Schwartz JH, LaBenz CJ, Gendelman HE. A regulatory role for astrocytes in HIV-1 encephalitis. J Immunol 154:3567–3581;1995.

    PubMed  Google Scholar 

  188. Nottet HSLM, Persidsky Y, Sasseville VG, Nukina AN, Bock P, Zhai Q-H, Sharer LR, McComb RD, Swindells S, Soderland C, Gendelman HE. Mechanisms for the transendothelial migration of HIV-1-infected monocytes in brain. J Immunol 156:1284–1295;1996.

    PubMed  Google Scholar 

  189. Nuovo GJ, Gallery F, MacConnell P, Braun A. In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acids and tumor necrosis factor-α RNA in the central nervous system. Am J Pathol 144:659–666;1994.

    PubMed  Google Scholar 

  190. Orsini MJ, Debouck CM, Webb CL, Lysko PG. Extracellular human immunodeficiency virus type 1 Tat protein promotes aggregation and adhesion of cerebellar neurons. J Neurosci 16:2546–2552;1996.

    PubMed  Google Scholar 

  191. del Pan GJ, McArthur JH, Aylward E, Selnes OA, Nance-Sproson TE, Kumar AJ, Mellits ED, McArthur JC. Patterns of cerebral atrophy in HIV-1-infected individuals: Results of a quantitative MRI analysis. Neurology 42:2125–2130;1992.

    PubMed  Google Scholar 

  192. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG. Glutamate-mediated astrocyte-neuron signaling. Nature 369:744–747;1994.

    Article  PubMed  Google Scholar 

  193. Patton HK, Benveniste EN, Benos DJ. Astrocytes and the AIDS dementia complex. J Neuro-AIDS 1:111–131;1996.

    Article  Google Scholar 

  194. Perrella O, Carrieri PB, Guarnaccia D, Soscia M. Cerebrospinal fluid cytokines and AIDS dementia complex. J Neurol 239:387–388;1992.

    PubMed  Google Scholar 

  195. Perry SW, HIV-related depression. In: Price RW, Perry SW, eds. HIV, AIDS and the Brain. New York, Raven Press, 223–238;1994.

    Google Scholar 

  196. Petito CK. Ependyma and choroid plexus. J Neuro-AIDS 1:101–110;1996.

    Article  Google Scholar 

  197. Pietraforte D, Tritarelli E, Testa U, Minetti M. gp120 HIV envelope glycoprotein increases the production of nitric oxide in human monocyte-derived macrophages. J Leukoc Biol 55:175–182;1994.

    PubMed  Google Scholar 

  198. Poland SD, Rice GPA, Dekaban GA. HIV-1 infection of human brain-derived microvascular endothelial cells in vitro. J Acquir Immune Defic Syndr Hum Retrovirol 8:437–445;1996.

    Google Scholar 

  199. Pomerantz RJ. 1966 (manuscript submitted).

  200. Poli G, Bressler P, Kinter A, Duh E, Timmer WC, Rabson A, Justement S, Stanley S, Fauci AS. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med 172:151–158;1990.

    Article  PubMed  Google Scholar 

  201. Power C, McArthur JC, Johnson RT, Griffin DE, Glass JD, Perryman S, Chesebro B. Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus tye 1 envelope sequences. J Virol 68:4643–4649;1994.

    PubMed  Google Scholar 

  202. Price RW, Brew B, Sidtis J, Rosenblum J, Scheck AC, Cleary P. The brain in AIDS: Central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–591;1988.

    PubMed  Google Scholar 

  203. Price RW, Brew BJ. The AIDS dementia complex. J Infect Dis 158:1079–1083;1988.

    PubMed  Google Scholar 

  204. Price RW. The cellular basis of central nervous system HIV-1 infection and the AIDS dementia complex. J Neuro-AIDS 1:1–20;1996.

    Article  Google Scholar 

  205. Puri RK, Aggarwal BB. Human immunodeficiency virus type 1tat gene upregulates interleukin 4 receptors on a human B-lymphoblastoid cell line. Cancer Res 52:3787–3790;1992.

    PubMed  Google Scholar 

  206. Pulliam L, West D, Haigwood N, Swanson RA. HIV-1 envelope gp120 alters astrocytes in human brain cultures. AIDS Res Hum Retroviruses 9:439–444;1993.

    PubMed  Google Scholar 

  207. Pumarola-Sune T, Navia BA, Cordon-Cardo C, Cho E-S, Price RW. HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol 21:490–496;1987.

    Article  PubMed  Google Scholar 

  208. Qiu Z, Parsons KL, Gruol DL. Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CNS neurons. J Neurosci 15:6688–6699;1995.

    PubMed  Google Scholar 

  209. Raff MC, Lisak RP, Gregson NA. Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture. Nature 274:813–816;1978.

    Google Scholar 

  210. Ranki A, Nyberg M, Ovod V, Haltia M, Elovaara I, Raininko R, Haapasalo H, Krohn K. Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 9:1001–1008;1995.

    PubMed  Google Scholar 

  211. Reddy RT, Achim CL, Sirko DA, Tehranchi S, Kraus FG, Wong-Staal F, Wiley CA, the HIV Neurobehavioral Research Group. Sequence analysis of the V3 loop in brain and spleen of patients with HIV encephalitis. AIDS Res Hum Retroviruses 12:477–482;1996.

    PubMed  Google Scholar 

  212. Resnick L, Shapshak P, Toutellote WW. Early penetration of the blood-brain barrier by HIV. Neurology 38:9–14;1988.

    Google Scholar 

  213. Robinson MB, Kjali S, Buchhalter JR. Inhibition of glutamate uptake withL-trans-pyrrolidine-2,4-dicarboxylate potentiates glutamate toxicity in primary hippocampal cultures. J Neurochem 61:2099–2103;1993.

    PubMed  Google Scholar 

  214. Rothstein JD, Jin L, Dykes-Hoberg M, Kuncl RW. Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity. Proc Natl Acad Sci USA 90:6591–6595;1993.

    Google Scholar 

  215. Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW. Localization of neuronal and glial glutamate transporters. Neuron 13:713–725;1994.

    Article  PubMed  Google Scholar 

  216. Rothenberg R, Woelfel M, Stoneburner R, Milberg J, Parker R, Truman B. Survival with the acquired immunodeficiency syndrome. Experience with 5833 cases in New York City. N Engl J Med 317:1297–1302;1987.

    PubMed  Google Scholar 

  217. Roubin R, Daegostini-Bazin H, Hirsch M-R, Goridis C. Modulation of NCAM expression by transforming growth factor-beta, serum, and autocrine factors. J Cell Biol 111:673–684;1990.

    Article  PubMed  Google Scholar 

  218. Rubenstein R, Price RW. Preservation of catecholamine uptake and release in herpes simplex virus type 1-infected PC12 cells. J Gen Virol 64:2505–2509;1983.

    PubMed  Google Scholar 

  219. Rytik RG, Eremin VF, Kvacheva ZB, Poleschuk NN, Popov SA, Schröder HC, Bachmann M, Weiler BE, Müller WEG. Susceptibility of primary human glial fibrillary acidic protein-positive brain cells to human immunodeficiency virus infection in vitro: Anti-HIV activity of memantine. AIDS Res Hum Retroviruses 7:89–95;1991.

    PubMed  Google Scholar 

  220. Saad B, Constam DB, Ortmann R, Moos M, Fontana A, Schachner M. Astrocyte-derived TGF-β2 and NGF differentially regulate neuronal recognition molecule expression by cultured astrocytes. J Cell Biol 115:473–484;1991.

    Article  PubMed  Google Scholar 

  221. Sabatier JM, Vives E, Mabrouk K, Benjouad A, Rochat H, Duval A, Hue B, Bahraoui E. Evidence for neurotoxic activity of Tat from HIV-1. J Virol 65:961–967;1991.

    PubMed  Google Scholar 

  222. Saito Y, Sharer LR, Epstein LG, Michaels J, Mintz M, Louder M, Golding K, Cvetkovich TA, Blumberg BM. Overexpression of Nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 44:474–481;1994.

    PubMed  Google Scholar 

  223. Sasseville VG, Newman WA, Lackner AA, Smith MO, Lausen NCG, Beall D, Ringler DJ. Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus. Am J Pathol 141:1021–1030;1992.

    PubMed  Google Scholar 

  224. Sasseville VG, Newman W, Brodie SJ, Hesterberg P, Pauley D, Ringler DJ. Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS encephalitis is mediated by vascular cell adhesion molecule-/α4β1 integrin interactions. Am J Pathol 144:27–40;1994.

    PubMed  Google Scholar 

  225. Sasseville VG, Lane JH, Walsh D, Ringler DJ, Lackner AA. VCAM-1 expression and leukocyte trafficking to the CNS occur early in infection with pathogenic isolates of SIV. J Med Primatol 24:123–131;1995.

    PubMed  Google Scholar 

  226. Sastry KJ, Reddy RHR, Pandita R, Totpal K, Aggarwal BB. HIV-1tat gene induces tumor necrosis factor-β (lymphotoxin) in a human B-lymphoblastoid cell line. J Biol Chem 265:20091–20093;1990.

    PubMed  Google Scholar 

  227. Schneider-Schaulies J, Schneider-Schaulies S, Brinkman R, Tas P, Halbrugge M, Walter U, Holmes HC, Ter Meulen V. HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase. Virology 191:765–772;1992.

    Article  PubMed  Google Scholar 

  228. Schwarcz R, Whetsell WO, Mangano RM. Quinolinic acid: An endogenous metabolite that produces axon-sparing lesions in rat brain. Science 219:316–318;1983.

    PubMed  Google Scholar 

  229. Segal M. Dendritic spines for neuroprotection. TINS 18:468–471;1995.

    PubMed  Google Scholar 

  230. Seilhean D, Duyckaerts C, Vazeux R, Bolgert F, Brunet P, Katlama C, Gentilini M, Hauw J-J. HIV-1-associated cognitive/motor complex: Absence of neuronal loss in the cerebral neocortex. Neurology 43:1492–1499;1993.

    PubMed  Google Scholar 

  231. Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23:339–346;1988.

    Article  PubMed  Google Scholar 

  232. Sharer LR, Epstein LG, Cho E-S, Joshi V-V, Meyenhofer MF, Rankin LF, Petito CK. Pathologic features of AIDS encephalopathy in children: Evidence for LAV/HTLV-III infection of brain. Hum Pathol 17:271–284;1986.

    PubMed  Google Scholar 

  233. Sharer LR, Prineas JW. Human immunodeficiency virus in glial cells? J Infect Dis 157:204;1988.

    Google Scholar 

  234. Sharer LR. Pathology of HIV-1 infection of the central nervous system. A review. J Neuropathol Exp Neurol 51:3–11;1992.

    PubMed  Google Scholar 

  235. Sharer LR. Neuropathology and pathogenesis of SIV infection of the central nervous system. In: Price RW, Perry SW, eds. HIV, AIDS and the Brain. New York, Raven Press, 133–146; 1994.

    Google Scholar 

  236. Sharief MK, Hentges R. Association between tumor necrosis factor-α and disease progression in patients with multiple sclerosis. N Engl J Med 325:467–472;1991.

    PubMed  Google Scholar 

  237. Sharpe AH, Hunter JJ, Chassier P, Jaenisch R. Role of abortive retroviral infection of neurons in spongiform CNS degeneration. Nature 346:181–183;1990.

    Article  PubMed  Google Scholar 

  238. Sharpless N, Gilbert D, Vandercam B, Zhou JM, Verdin E, Ronnett G, Friedman E, Dubois-Dalcq M. The restricted nature of HIV-1 tropism for cultured neural cells. Virology 191:813–825;1992.

    Article  PubMed  Google Scholar 

  239. Shimizu NS, Shimizu NG, Takeuchi Y, Hoshino H. Isolation and characterization of human immunodeficiency virus type 1 variants infectious to brain-derived cells: Detection of common point mutations in the V3 region of theenv gene of the variants. J Virol 68:6130–6135;1994.

    PubMed  Google Scholar 

  240. Sidtis JJ. Evaluation of the AIDS dementia complex in adults. In: Price RW, Perry SW, eds. HIV, AIDS and the Brain. New York, Raven Press, 273–287;1994.

    Google Scholar 

  241. Simmonds P. Neurotropism of HIV type 1? AIDS Res Hum Retroviruses 12:469–470;1996.

    Google Scholar 

  242. Sinclair E, Gray F, Ciardi A, Scaravilli F. Immunohistochemical changes and PCR detection of HIV provirus DNA in brains of asymptomatic HIV-positive patients. J Neuropathol Exp Neurol 53:43–50;1994.

    PubMed  Google Scholar 

  243. Skrikant P, Benos DJ, Tang L-P, Benveniste EN. HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells. J Immunol 156:1307–1314;1996.

    PubMed  Google Scholar 

  244. Sloan DJ, Wood MJ, Charlton HM. Leucocyte recruitment and inflammation in the CNS. TINS 15:276–278;1992.

    PubMed  Google Scholar 

  245. Snyder SS. Nitric oxide: First in a new class of neurotransmitters? Science 257:494–496;1992.

    Google Scholar 

  246. Spector SA, Hsia K, Pratt D, Lathey J, McCutchan JA, Alcaraz JE, Atkinson JH, Gulevich S, Wallace M, Grant I, HIV Neurobehavioral Res Center Group. Virologic markers of human immunodeficiency virus type 1 in cerebrospinal fluid. J Infect Dis 168:68–74;1993.

    PubMed  Google Scholar 

  247. Sporn MB, Robers AB, Wakefield LM, de Crombrugghe B. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 105:1039–1045;1987.

    Article  PubMed  Google Scholar 

  248. Stefano GB, Sawada M, Smith EM, Hughes TK. Selective effects of human immunodeficiency virus (HIV) gp120 on invertebrate neurons. Cell Mol Neurobiol 13:569–577;1994.

    Article  Google Scholar 

  249. Stephens EB, Liu Z-Q, Zhu G-W, Adany I, Joag SV, Foresman L, Berman NEJ, Narayan O. Lymphocyte-tropic simian immunodeficiency virus causes persistent infection in the brains of rhesus monkeys. Virology 213:600–614;1995.

    Article  PubMed  Google Scholar 

  250. Subramanyam M, Gutheil WG, Bachovchin WW, Huber BT. Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness. J Immunol 150:2544–2553;1993.

    PubMed  Google Scholar 

  251. Tardieu M, Héry C, Peudenier S, Boespflug O, Montagnier L. Human immunodeficiency virus type 1-infected monocytic cells can destroy human neural cells after cell-to-cell adhesion. Ann Neurol 32:11–17;1992.

    Article  PubMed  Google Scholar 

  252. Tardieu M, Janabi N. HIV-1 and the developing human nervous system: In vivo and in vitro aspects. Dev Neurosci 16:137–144;1944.

    Google Scholar 

  253. Taylor JP, Cupp C, Diaz A, Chowdhury M, Khalili K, Jimenez SA, Amini S. Activation of expression of genes coding for extracellular matrix proteins in Tat-producing glioblastoma cells. Proc Natl Acad Sci USA 89:9617–9621;1992.

    PubMed  Google Scholar 

  254. Taylor JP, Pomerantz RJ, Raj GV, Kashanchi F, Brady JN, Amini S, Khalili K. Central nervous system-derived cells express a κB-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat. J Virol 68:3971–3981;1994.

    PubMed  Google Scholar 

  255. Teoh R, Humphries M. Tuberculous meningitis. In Lambert HP, ed. Infections of the Central Nervous System. Philadelphia, Decker, 189–207;1991.

    Google Scholar 

  256. Thomas FP, Chalk C, Lalonde R, Robitaille Y, Jolicoeur P. Expression of human immunodeficiency virus type 1 in the nervous system of transgenic mice leads to neurological disease. J Virol 68:7099–7107;1994.

    PubMed  Google Scholar 

  257. Toggas SM, Masliah E, Rockenstein EM, Rall GF, Abraham CR, Mucke L. Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature 367:188–193;1994.

    Article  PubMed  Google Scholar 

  258. Tong G, Jahr CE. Block of glutamate transporters potentiates postsynaptic excitation. Neuron 13:1195–1203;1994.

    Article  PubMed  Google Scholar 

  259. Tornatore C, Nath A, Amemiya K, Major EO. 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 65:6094–6100;1993.

    Google Scholar 

  260. Tornatore C, Chandra R, Berger JR, Major EO. HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 44:481–487;1994.

    PubMed  Google Scholar 

  261. Treisman G, Fishman M, Lyketsos C, McHugh PR. Evaluation and treatment of psychiatric disorders associated with HIV infection. In: Price RW, Perry SW, eds. HIV, AIDS and the Brain. New York, Raven Press, 239–250;1994.

    Google Scholar 

  262. Trottei D, Volterra A, Lehre KP, Rossi D, Gjesdai O, Racagni G, Danbolt NC. Arachidonic acid inhibits a purified and reconstituted glutamate transporter directly from the water phase and not via the phospholipid membrane. J Biol Chem 270:9890–9895;1995.

    Article  PubMed  Google Scholar 

  263. Truckenmiller ME, Kulaga H, Coggiano M, Wyatt R, Snyder SH, Sweetnam PM. Human cortical neuronal cell line: A model for HIV-1 infection in an immature neuronal system. AIDS Res Hum Retroviruses 9:445–453;1993.

    PubMed  Google Scholar 

  264. Trujillo JR, Wang W-K, Lee T-H, Essex M. Identification of the envelope V3 loop as a determinant of a CD4-negative neuronal cell tropism for HIV-1. Virology 217:613–617;1996.

    Article  PubMed  Google Scholar 

  265. Tyor WR, Glass JD, Triffin JW, Becker PS, McArthur JC, Bezman L, Griffin D. Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol 31:349–360;1992.

    Article  PubMed  Google Scholar 

  266. Vesanen M, Salminen M, Wessman M, Lankinen H, Sistonen P, Vaheri A. Morphological differentiation of human SH-SY5Y neuroblastoma cells inhibits human immunodeficiency virus type 1 infection. J Gen Virol 75:201–206;1994.

    PubMed  Google Scholar 

  267. Vinters HV. Neuropathology. Ann Intern Med 111:400–410;1989.

    PubMed  Google Scholar 

  268. Vitkovic L, Wood GP, Major EO, Fauci AS. Human astrocytes stimulate HIV-1 expression in a chronically infected promonocyte clone via interleukin-5. AIDS Res Hum Retroviruses 7:723–727;1991.

    PubMed  Google Scholar 

  269. Vogel BE, Lee S-J, Hildebrand A, Craig W, Pierschbacher MD, Wong-Staal F, Ruoslahti E. A novel integrin specificity exemplified by binding of the ανβ5 integrin to the basic domain of the HIV Tat protein and vitronectin. J Cell Biol 121:461–468;1993.

    Article  PubMed  Google Scholar 

  270. Volsky B, Sakai K, Reddy MM, Volsky DJ. A system for the high efficiency replication of HIV-1 in neural cells and its application to anti-viral evaluation. Virology 186:303–308;1992.

    Article  PubMed  Google Scholar 

  271. Volterra A, Trotti D, Cassutti P, Tromba C, Salvaggio A, Melcangi RC, Racagni G. High sensitivity of glutamate uptake to extracellular free arachidonic acid levels in rat cortical synaptosomes and astrocytes. J Neurochem 59:600–606;1992.

    PubMed  Google Scholar 

  272. Volterra A, Trotti D, Racagni G. Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms. Mol Pharmacol 46:986–992;1994.

    PubMed  Google Scholar 

  273. Vornov JJ, Tasker RC, Park J. Neurotoxicity of acute glutamate transport blockade depends on coactivation of both NMDA and AMPA/kainate receptors in organotypic hippocampal cultures. Exp Neurol 133:7–17;1995.

    Article  PubMed  Google Scholar 

  274. Ursini MV, Lettieri T, Braddock M, Martini G. Enhanced activity of human G6PD promoter transfected in HeLa cells producing high levels of HIV-1 Tat. Virology 196:338–343;1993.

    Article  PubMed  Google Scholar 

  275. Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB. Transforming growth factor type b induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 84:5788–5792;1987.

    PubMed  Google Scholar 

  276. Wahl SM, Allen JB, McCartney-Francis N, Morganti-Kossmann MC, Kossmann T, Ellingsworth L, Mai UEH, Mergenhagen SE, Orenstein JM. Macrophage- and astrocyte-derived transforming growth factor β as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. J Exp Med 173:981–991;1991.

    Article  PubMed  Google Scholar 

  277. Watry D, Lant TE, Streb M, Fox HS. Transfer of neuropathogenic siminan immunodeficiency virus with naturally infected microglia. Am J Pathol 146:914–923;1995.

    PubMed  Google Scholar 

  278. Weber J, Clapham P, McKeating J, Stratton M, Robey E, Weiss R. Infection of brain cells by diverse human immunodeficiency virus isolates: Role of CD4 as receptor. J Gen Virol 70:2653–2660;1989.

    PubMed  Google Scholar 

  279. Weeks BS, Desai K, Loewenstein PM, Klotman ME, Klotman PE, Green M, Kleinman HK. Identification of a novel cell attachment domain in the HIV-1 Tat protein and its 90-kDa cell surface binding protein. J Biol Chem 268:5279–5284;1993.

    PubMed  Google Scholar 

  280. Weeks BS, Lieberman DM, Johnson B, Roque E, Green M, Loewenstein P, Oldfield EH, Kleinman HK. Neurotoxicity of the human immunodeficiency virus type 1 Tat transactivator to PC12 cells requires the Tat amino acid 49–58 basic domain. J Neurosci Res 42:34–40;1995.

    Article  PubMed  Google Scholar 

  281. Weidenheim KM, Epshteyn I, Lyman WD. Immunocytochemical identification of T-cells in HIV-1 encephalitis: Implications for pathogenesis of CNS disease. Mod Pathol 6:167–174;1993.

    PubMed  Google Scholar 

  282. Werner T, Ferroni S, Saermark T, Brack-Werner R, Bannati RB, Mager R, Steinaa L, Kreutzberg GW, Erfle V. HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels. AIDS 5:1301–1308;1991.

    PubMed  Google Scholar 

  283. Wesselingh SL, Power C, Glass JD, Tyor WR, McArthur JC, Farber JM, Griffin JW, Griffin DE. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol 33:576–582;1993.

    Article  PubMed  Google Scholar 

  284. Westendorp MO, Li-Weber M, Frank RW, Krammer PH. Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. J Virol 68:4177–4185;1994.

    PubMed  Google Scholar 

  285. Westmoreland SV, Kolson D, Gonzalez-Scarano F. Toxicity of TNFα and platelet activating factor for human NT2N neurons: A tissue culture model for human immunodeficiency virus dementia. J Neurovirol 2:118–126;1996.

    PubMed  Google Scholar 

  286. Whetsell WO, Schwarcz R. Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system. Neurosci Lett 97:271–275;1989.

    Article  PubMed  Google Scholar 

  287. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MBA. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 83:7089–7093;1986.

    PubMed  Google Scholar 

  288. Wiley CA, Masliah E, Morey M, Lemere C, DeTeresa R, Grafe M, Hansen L, Terry R. Neocortical damage during HIV infection. Ann Neurol 29:651–657;1991.

    Article  PubMed  Google Scholar 

  289. Wiley CA, Achim CL, Schrier RD, Heyes MP, McCutchan JA, Grant I. Relationship of cerebrospinal fluid immune activation associated factors to HIV encephalitis. AIDS 6:1299–1307;1992.

    PubMed  Google Scholar 

  290. Wiley CA, Achim C. Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome. Ann Neurol 36:673–676;1994.

    Article  PubMed  Google Scholar 

  291. Williams KC, Hickey WF. Traffic of lymphocytes into the CNS during inflammation and HIV infection. J Neuro-AIDS 1:31–55;1996.

    Article  Google Scholar 

  292. Wilt SG, Milward E, Zhou JM, Nagasato K, Patton H, Rusten R, Griffin DE, O'Connor M, Dubois-Dalcq M. In vitro evidence for a dual role of tumor necrosis factor-α in human immunodeficiency virus type 1 encephalopathy. Ann Neurol 37:381–394;1995.

    Article  PubMed  Google Scholar 

  293. Xin L, Blatteis CM. Hypothalamic neuronal responses to interleukin-6 in tissue slices: Effects of indomethacin and naloxone. Brain Res Bull 29:27–35;1992.

    Article  PubMed  Google Scholar 

  294. Yamato K, El-Hajjaoui Z, Simon K, Phillip Koeffler H. Modulation of interleukin-1β RNA in monocytic cells infected with human immunodeficiency virus-1. J Clin Invest 86:1109–1114;1990.

    PubMed  Google Scholar 

  295. Yeung MC, Pulliam L, Lau AS. The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-α. AIDS 9:137–143;1995.

    PubMed  Google Scholar 

  296. Zajicek JP, Wing M, Scolding NJ, Compston DAS. Interactions between oligodendrocytes and microglia. Brain 115:1611–1631;1992.

    PubMed  Google Scholar 

  297. Zauli G, Davis BR, Re MC, Visani G, Furlini G, La Placa M. Tat protein stimulates production of transforming growth factor-β1 by marrow macrophages: A potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression. Blood 80:3036–3043;1992.

    PubMed  Google Scholar 

  298. Zielasek J, Tauschi M, Toyka KV, Hartung H-P. Production of nitrite by neonatal rat microglial cell/brain macrophages. Cell Immunol 141:111–120;1992.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Neurology and Microbiology, University of Pennsylvania Medical Center, USA

    Dennis L. Kolson MD, PhD

  2. The Dorrance H. Hamilton Laboratories, Center for Human Retrovirology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa., USA

    Roger J. Pomerantz

Authors
  1. Dennis L. Kolson MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roger J. Pomerantz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kolson, D.L., Pomerantz, R.J. AIDS dementia and HIV-1-induced neurotoxicity: Possible pathogenic associations and mechanisms. J Biomed Sci 3, 389–414 (1996). https://doi.org/10.1007/BF02258044

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02258044

Key Words

Search

Navigation