Hostname: page-component-76fb5796d-45l2p Total loading time: 0 Render date: 2024-04-26T18:23:18.974Z Has data issue: false hasContentIssue false
  • English
  • Français

HIV-1 Associated Dementia: Clinical Features and Pathogenesis

Published online by Cambridge University Press:  18 September 2015

Christopher Power  and
Richard T. Johnson
Christopher Power*
Affiliation:
Department of Neurology, Johns Hopkins University. Baltimore
Richard T. Johnson
Affiliation:
Department of Neurology, Johns Hopkins University. Baltimore
*
Section of Neurology, Department of Internal Medicine, University of Manitoba, GF 543, Health Sciences Centre. 700 William Street, Winnipeg, Maniboba, Canada R3E 0Z3
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

HIV-1 infection is characterized by multiple neurological syndromes occuring at all stages of infection. HIV-1-associated dementia, however, is the most devastating CNS consequence of AIDS because of its poor prognosis and functional impairment. A clinical triad of progressive cognitive decline, motor dysfunction, and behavioural abnormalities typifies this subcortical dementia which eventually affects 15 to 20% of AIDS patients. Neuroimaging, CSF studies and neuropsychological testing are frequently required in diagnosing HIV-associated dementia, to exclude other conditions including psychiatric illnesses, opportunistic diseases and systemic disorders. The pathogenesis of HIV dementia is uncertain and there is evidence that multiple mechanisms of neurological injury occur. These mechanisms include: the role of neurovirulent strains of HIV; the potential neurotoxicity of HIV gp120, nitric oxide and quinolinic acid; immunologically mediated CNS injury through the action of cytokines and arachidonic acid metabolites; and altered blood-brain barrier permeability. A collective approach involving clinical studies, in vitro assays and animal models will provide greater insight into the pathogenesis and the rational development of therapy for HIV dementia.

Type
Review Articles
Information
Canadian Journal of Neurological Sciences , Volume 22 , Issue 2 , May 1995 , pp. 92 - 100
Copyright
Copyright © Canadian Neurological Sciences Federation 1995

References

1.Merson, MH.Slowing the spread of HIV: agenda for the 1990s. Science 1993; 260: 1266–1268.CrossRefGoogle ScholarPubMed
2.Pedersen, NC., Ho, EW., Brown, ML., Yamamoto, JK.Isolation of a Tlymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science 1987; 235: 790–793.CrossRefGoogle ScholarPubMed
3.Narayan, O., Clements, JE.Biology and pathogenesis of lentiviruses. J Gen Virol 1989; 70: 1617–1639.CrossRefGoogle ScholarPubMed
4.Curran, JW., Morgan, WM., Hardy, AM., et al. The epidemiology of AIDS: current status and future prospects. Science 1985; 229: 1352–1357.CrossRefGoogle ScholarPubMed
5.Myers, G., Wain-Hobson, S., Korber, B., Smith, RF.Human Retroviruses and AIDS 1993. A Compilation and Analysis of Nucleic Acid and Amino Acid Sequences. Theoretical Biology and Biophysics Group T-10, 1993; Los Alamos, NM,Google Scholar
6.Clavel, F., Guetard, D., Brun-Vezinet, F., et al. Isolation of a new human retrovirus from West African patients with AIDS. Science 1986; 233: 343–346.CrossRefGoogle ScholarPubMed
7.Clavel, F., Mansinho, K., Chamaret, S., et al. Human immunodeficiency virus type 2 infection associated with AIDS in West Africa. N Engl J Med 1987; 316: 1180–1185.CrossRefGoogle ScholarPubMed
8.Barre-Sinoussi, F., Chermann, JC., Rey, F., et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983; 220: 868–871.CrossRefGoogle ScholarPubMed
9.Kong, LI., Lee, SW., Kappes, JC., et al. West African HIV-2-related human retrovirus with attenuated cytopathicity. Science 1988; 240: 1525–1529.CrossRefGoogle ScholarPubMed
10.Chaisson, RE., Volberding, PA.Clinical manifestations of HIV infection. In: Mandell, GL., Douglas, RG Jr., Bennett, JE., eds. Principles and Practice of Infectious Diseases, 3rd edn. New York: Churchill Livingstone, 1990; 1059.Google Scholar
11.Belman, AL., Diamond, G., Dickson, D., et al. Pediatric acquired immunodeficiency syndrome. Neurologic syndromes [published erratum appears in Am J Dis Child 1988 May; 142(5):507]. Am J Dis Child 1988; 142:29–35.CrossRefGoogle Scholar
12.Levy, RM., Rosenbloom, S., Perrett, LV.Neuroradiologic findings in AIDS: a review of 200 cases. Am J Roentgenol 1986; 147: 977–983.CrossRefGoogle Scholar
13.Gabuzda, DH., Hirsch, MS.Neurologic manifestations of infection with human immunodeficiency virus. Clinical features and pathogenesis. Ann Intern Med 1987; 107: 383–391.CrossRefGoogle ScholarPubMed
14.Johnson, RT., McArthur, JC., Narayan, O.The neurobiology of human immunodeficiency virus infections. FASEB J 1988; 2: 2970–2981.CrossRefGoogle ScholarPubMed
15.Giulian, D., Vaca, K., Corpuz, M.Brain glia release factors with opposing actions upon neuronal survival. J Neurosci 1993; 13: 29–37.CrossRefGoogle ScholarPubMed
16.McArthur, JC.Neurologic manifestations of AIDS. Medicine 1987; 66: 407–437.CrossRefGoogle ScholarPubMed
17.Janssen, RS., Cornblath, DR., Epstein, LG., et al. Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology 1991; 41: 778–785.Google Scholar
18.Navia, BA., Cho, E-S., Petito, CK., Price, RW.The AIDS dementia complex: II. Neuropathology. Ann Neurol 1986; 19: 525–535.CrossRefGoogle ScholarPubMed
19.Navia, BA., Jordan, BD., Price, RW.The AIDS dementia complex: I. Clinical features. Ann Neurol 1986; 19: 517–524.CrossRefGoogle ScholarPubMed
20.Janssen, RS., Nwanyanwu, OC., Selik, RM., Stehr-Green, JK.Epidemiology of human immunodeficiency virus encephalopathy in the United States. Neurology 1992; 42: 1472–1476.CrossRefGoogle ScholarPubMed
21.McArthur, JC., Cohen, BA., Selnes, OA., et al. Low prevalence of neurological and neuropsychological abnormalities in otherwise healthy HIV-1-infected individuals: results from the multicenter AIDS Cohort Study. Ann Neurol 1989; 26: 601–611.CrossRefGoogle ScholarPubMed
22.Goethe, KE., Mitchell, JE., Marshall, DW., et al. Neuropsychological and neurological function of human immunodeficiency virus seropositive asymptomatic individuals. Arch Neurol 1989; 46: 129–133.CrossRefGoogle ScholarPubMed
23.Selnes, OA., Miller, E., McArthur, J., et al. HIV-1 infection: no evidence of cognitive decline during the asymptomatic stages. The Multicenter AIDS Cohort Study [see comments]. Neurology 1990; 40: 204–208.CrossRefGoogle ScholarPubMed
24.McArthur, JC., Hoover, DR., Bacellar, H., et al. Dementia in AIDS patients: incidence and risk factors. Neurology 1993; 43: 2245–2252.CrossRefGoogle ScholarPubMed
25.Price, RW., Brew, BJ.The AIDS dementia complex. J Infect Dis 1988; 158: 1079–1083.CrossRefGoogle ScholarPubMed
26.Tross, S., Price, RW., Navia, B., et al. Neuropsychological characterization of the AIDS dementia complex: a preliminary report. AIDS 1988; 2: 81–88.CrossRefGoogle ScholarPubMed
27.Power, C., Selnes, OA., Grim, JA., McArthur, JC.The HIV dementia scale: a rapid screening test. J Acquir Immune Defic Syndr Hum Retrovir 1995; 8: 273–278.CrossRefGoogle Scholar
28.Folstein, MF., Folstein, SE., McHugh, PR.Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–198.CrossRefGoogle Scholar
29.Currie, J., Benson, E., Ramsden, B., Perdices, M., Cooper, D.Eye movement abnormalities as a predictor of the acquired immunodeficiency syndrome dementia complex (see comments]. Arch Neurol 1988; 45: 949–953.CrossRefGoogle Scholar
30.McArthur, JC., Sipos, E., Cornblath, DR., et al. Identification of mononuclear cells in CSF of patients with HIV infection. Neurology 1989; 39: 66–70.CrossRefGoogle ScholarPubMed
31.Royal, W., Selnes, OA., Concha, M., Nance-Sproson, TE., McArthur, JC.Cerebrospinal fluid HIV-1 p24 antigen levels in HIV-1-related dementia. Ann Neurol 1994; 36: 32–39.CrossRefGoogle ScholarPubMed
32.Post, MJ., Tate, LG., Quencer, RM., et al. CT, MR, and pathology in HIV encephalitis and meningitis. Am J Roentgenol 1988; 151: 373–380.CrossRefGoogle ScholarPubMed
33.LaFrance, ND., Pearlson, GD., Schaerf, FW., et al. 1–123 IMP-SPECT in HIV-related dementia. Ad Funct Neuroimaging 1988; 1:9–15.Google Scholar
34.Koralnik, IJ., Beaumanoir, A., Hausler, R., et al. A controlled study of early neurologic abnormalities in men with asymptomatic human immunodeficiency virus infection [published erratum appears in N Engl J Med 1990 Dec 13;323(24): 1716] [see comments]. N Engl J Med 1990; 323: 864–870.CrossRefGoogle Scholar
35.Holland, NR., Power, C., Mathews, VP., et al. Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS). Neurology 1994; 44: 507–514.CrossRefGoogle ScholarPubMed
36.Glass, JD., Wesselingh, SL., Selnes, OA., McArthur, JC.Clinical-neuropathologic correlation in HIV-associated dementia. Neurology 1993; 43: 2230–2237.CrossRefGoogle ScholarPubMed
37.Gray, F., Gherardi, R., Scaravilli, F.The neuropathology of the acquired immune deficiency syndrome (AIDS). A review. Brain 1988; 111:245–266.Google ScholarPubMed
38.Davis, LE., Hjelle, BL., Miller, VE., et al. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology 1992, 42: 1736–1739.CrossRefGoogle ScholarPubMed
39.Gray, F., Lescs, MC., Keohane, C., et al. Early brain changes in HIV infection: neuropathological study of 11 HIV seropositive, non-AIDS cases. J Neuropathol Exp Neurol 1992; 51:177–185.CrossRefGoogle ScholarPubMed
40.Budka, H.Neuropathology of human immunodeficiency virus infection. Brain Pathol 1991; 1: 163–175.CrossRefGoogle ScholarPubMed
41.Vinters, HV., Anders, KH.Neuropathology of AIDS. Boca Raton: CRC Press, 1990; 197.Google Scholar
42.Sharer, LR.Pathology of HIV-1 infection of the central nervous system. A review. J Neuropathol Exp Neurol 1992; 51:3–11.CrossRefGoogle ScholarPubMed
43.Everall, IP., Luthert, PJ., Lantos, PL.Neuronal loss in the frontal cortex in HIV infection [see comments]. Lancet 1991; 337: 1119–1121.CrossRefGoogle ScholarPubMed
44.Gray, F., Haug, H., Chimelli, L., et al. Prominent cortical atrophy with neuronal loss as correlate of human immunodeficiency virus encephalopathy. Acta Neuropathol (Berl) 1991; 82: 229–233.CrossRefGoogle Scholar
45.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 1986; 83: 7089–7093.CrossRefGoogle ScholarPubMed
46.Shaw, GM., Harper, ME., Hahn, BH., et al. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 1985; 227: 177–182.CrossRefGoogle ScholarPubMed
47.Koenig, S., Gendelman, HE., Orenstein, JM., et al. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 1986; 233: 1089–1093.CrossRefGoogle ScholarPubMed
48.Kure, K., Weidenheim, KM., Lyman, WD., Dickson, DW.Morphology and distribution of HIV-I gp41-positive microglia in subacute AIDS encephalitis. Pattern of involvement resembling a multisystem degeneration. Acta Neuropathol (Berl) 1990; 80: 393–400.CrossRefGoogle ScholarPubMed
49.Pumarola-Sune, T., Navia, BA., Cordon-Cardo, C., Cho, ES., Price, RW.HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol 1987; 21: 490–496.CrossRefGoogle ScholarPubMed
50.Watkins, BA., Dorn, HH., Kelly, WB., et al. Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science 1990; 249: 549–553.CrossRefGoogle ScholarPubMed
51.Yamada, M., Watabe, K., Saida, T., Kim, SU.Increased susceptibility of human fetal astrocytes to human T-lymphotropic virus type I in culture. J Neuropathol Exp Neurol 1991; 50: 97–107.CrossRefGoogle ScholarPubMed
52.Vazeux, R., Lacroix-Ciaudo, C., Blanche, S., et al. Low levels of human immunodeficiency virus replication in the brain tissue of children with severe acquired immunodeficiency syndrome encephalopathy. Am J Pathol 1992; 140: 137–144.Google ScholarPubMed
53.Nuovo, GJ., Gallery, F., MacConnell, P., Braun, A.In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acids and tumor necrosis factor-alpha RNA in the central nervous system. Am J Pathol 1994; 144: 659–666.Google ScholarPubMed
54.Wiley, CA., Masliah, E., Morey, M., et al. Neocortical damage during HIV infection. Ann Neurol 1991; 29: 651–657.CrossRefGoogle ScholarPubMed
55.Masliah, E., Ge, N., Morey, M., et al. Cortical dendritic pathology in human immunodeficiency virus encephalitis [see comments]. Lab Invest 1992; 66: 285–291.Google ScholarPubMed
56.Masliah, E., Ge, N., Achim, CL., Hansen, LA., Wiley, CA.Selective neuronal vulnerability in HIV encephalitis. J Neuropathol Exp Neurol 1992; 51: 585–593.CrossRefGoogle ScholarPubMed
57.Portegies, P., de Gans, J., Lange, JM., et al. Declining incidence of AIDS dementia complex after introduction of zidovudine treatment [published erratum appears in Br Med J 1989 Nov 4; 299(6708): 1141] [see comments]. Br Med J 1989; 299: 819–821.CrossRefGoogle Scholar
58.Schmitt, FA., Bigley, JW., McKinnis, R., et al. Neuropsychological outcome of zidovudine (AZT) treatment of patients with AIDS and AIDS-related complex. N Engl J Med 1988; 319: 1573–1578.CrossRefGoogle ScholarPubMed
59.Sidtis, JJ., Gatsonis, C., Price, RW., et al. Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group. Ann Neurol 1993; 33: 343–349.CrossRefGoogle ScholarPubMed
60.Pizzo, PA., Eddy, J., Falloon, J., et al. Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection [see comments]. N Engl J Med 1988; 319: 889–896.CrossRefGoogle ScholarPubMed
61.Dreyer, EB., Kaiser, PK., Offermann, JT., Lipton, SA.HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 1990; 248: 364–367.CrossRefGoogle ScholarPubMed
62.Heyes, MP., Brew, BJ., Martin, A., et al. Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol 1991; 29: 202–209.CrossRefGoogle ScholarPubMed
63.Tyor, WR., Glass, JD., Griffin, JW., et al. Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol 1992; 31: 349–360.CrossRefGoogle ScholarPubMed
64.Wesselingh, SL., Power, C., Glass, JD., et al. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol 1993; 33: 576–582.CrossRefGoogle ScholarPubMed
65.Li, Y., Kappes, JC., Conway, JA., et al. Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes. J Virol 1991; 65: 3973–3985.CrossRefGoogle ScholarPubMed
66.Li, Y., Hui, H., Burgess, CJ., et al. Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation. J Virol 1992; 66: 6587–6600.CrossRefGoogle ScholarPubMed
67.Pang, S., Vinters, HV., Akashi, T., O’Brien, WA., Chen, ISY.HIV-1 Env sequence variation in brain tissue of patients with AIDS-related neurologic disease. J Acquir Immune Defic Syndr 1991; 4: 1082–1092.Google ScholarPubMed
68.Epstein, LG., Kuiken, C., Blumberg, BM., et al. HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies. Virology 1991; 180:583–590.CrossRefGoogle ScholarPubMed
69.Giulian, D., Vaca, K., Noonan, C.Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1. Science 1990: 250: 1593–1596.CrossRefGoogle ScholarPubMed
70.Haase, AT.Pathogenesis of lentivirus infections. Nature 1986; 322: 130–136.CrossRefGoogle ScholarPubMed
71.Dalgleish, AG., Beverley, PC., Clapham, PR., et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984; 312: 763–767.CrossRefGoogle ScholarPubMed
72.Harouse, JM., Bhat, S., Spitalnik, SL., et al. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science 1991; 253: 320–323.CrossRefGoogle ScholarPubMed
73.Ma, M., Geiger, J., Nath, A.Characterization of a novel binding site for the human immunodeficiency virus type 1 envelope protein gp120 on fetal astrocytes. J Virol 1994; 68: 6824–6828.CrossRefGoogle ScholarPubMed
74.Moses, AV., Bloom, FE., Pauza, CD., Nelson, JA.Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism. Proc Natl Acad Sci USA 1993; 90: 10474–10478.CrossRefGoogle Scholar
75.Chesebro, B., Nishio, J., Perryman, S., et al. Identification of human immunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells, and macrophages. J Virol 1991; 65: 5782–5789.CrossRefGoogle ScholarPubMed
76.Sharpless, NE., O’Brien WA, Verdin, E., et al. Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism. J Virol 1992; 66: 2588–2593.CrossRefGoogle ScholarPubMed
77.Shioda, T., Levy, JA., Cheng-Mayer, C.Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp 120 gene. Nature 1991; 349: 167–169.CrossRefGoogle Scholar
78.Koyanagi, Y., Miles, S., Mitsuyasu, RT., et al. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 1987; 236: 819–822.CrossRefGoogle ScholarPubMed
79.Georgsson, G., Houwers, DJ., Pálsson, PA., Pétursson, G.Expression of viral antigens in the central nervous system of visna-infected sheep: an immunohistochemical study on experimental visna induced by virus strains of increased neurovirulence. Acta Neuropathol 1989; 77: 299–306.CrossRefGoogle Scholar
80.Sharma, DP., Zink, MC., Anderson, M., et al. Derivation of neurotropic simian immunodeficiency virus from exclusively lymphocytetropic parental virus: pathogenesis of infection in macaques. J Virol 1992; 66: 3550–3556.CrossRefGoogle ScholarPubMed
81.Lynch, WP., Czub, S., McAtee, FJ., Hayes, SF., Portis, JL.Murine retrovirus-induced spongiform encephalopathy: productive infection of microglia and cerebellar neurons in accelerated CNS disease. Neuron 1991; 7: 365–379.CrossRefGoogle ScholarPubMed
82.Szurek, PF., Floyd, E., Yuen, PH., Wong, PKY.Site-directed mutagenesis of the codon for Ile-25 in gPr80cm alters the neurovirulence of ts1, a mutant of Moloney murine leukemia virus TB. J Virol 1990; 64: 5241–5429.CrossRefGoogle ScholarPubMed
83.Lackner, AA., Dandekar, S., Gardner, MB.Neurobiology of simian and feline immunodeficiency virus infections. Brain Pathol 1991; 1:201–212.CrossRefGoogle ScholarPubMed
84.Nathanson, N., Georgsson, G., Palsson, PA., et al. Experimental visna in Icelandic sheep: the prototype lentiviral infection. Rev Infect Dis 1985; 7: 75–82.CrossRefGoogle ScholarPubMed
85.Power, C., McArthur, JC., Johnson, RT., et al. Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J Virol 1994; 68: 4643–4649.CrossRefGoogle ScholarPubMed
86.Giulian, D., Wendt, E., Vaca, K., Noonan, CA.The envelope glycoprotein of human immunodeficiency virus type I stimulates release of neurotoxins from monocytes. Proc Natl Acad Sci USA 1993; 90: 2769–2773.CrossRefGoogle ScholarPubMed
87.Power, C., McArthur, JC., Johnson, RT., et al. Distinct HIV-1 env sequences are associated with neurotropism and neurovirulence. Curr Top Microbiol Immunol; (In Press).Google Scholar
88.Merrill, JE., Chen, IS.HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB J 1991; 5: 2391–2397.CrossRefGoogle ScholarPubMed
89.Lipton, SA.HIV-related neurotoxicity. Brain Pathol 1991; 1: 193–199.CrossRefGoogle ScholarPubMed
90.Hill, JM., Mervis, RF., Avidor, R., Moody, TW., Brenneman, DE.HIV envelope protein-induced neuronal damage and retardation of behavioral development in rat neonates. Brain Res 1993; 603: 222–233.CrossRefGoogle ScholarPubMed
91.Dawson, VL., Dawson, TM., 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 1993; 90: 3256–3259.CrossRefGoogle ScholarPubMed
92.Rosenberg, ZF., Fauci, AS.Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. Immunol Today 1990; II: 176–180.CrossRefGoogle Scholar
93.Power, C., Kong, P-A., Crawford, TO., et al. Cerebral white matter changes in acquired immunodeficiency syndrome dementia: alterations of the blood-brain barrier. Ann Neurol 1993; 34: 339–350.CrossRefGoogle ScholarPubMed
94.Merrill, JE., Koyanagi, Y., Chen, IS.Interleukin-I and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type I binding to the CD4 receptor. J Virol 1989; 63: 4404–4408.CrossRefGoogle Scholar
95.Mintz, M., Rapaport, R., Oleske, JM., et al. Elevated serum levels of tumor necrosis factor are associated with progressive encephalopathy in children with acquired immunodeficiency syndrome. Am J Dis Child 1989; 143: 771–774.Google ScholarPubMed
96.Genis, P., Jett, M., Bernton, EW., et al. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med 1992; 176: 1703–1718.CrossRefGoogle ScholarPubMed
97.Griffin, DE., Wesselingh, SL., McArthur, JC.Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia. Ann Neurol 1994; 35: 592–597.CrossRefGoogle ScholarPubMed
98.Selmaj, KW., Raine, CS.Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988; 23: 339–346.CrossRefGoogle ScholarPubMed
99.Quagliarello, VJ., Wispelwey, B., Long, WJ Jr., Scheld, WM.Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. J Clin Invest 1991; 87: 1360–1366.CrossRefGoogle ScholarPubMed
100.Ramilo, O., Saez-Llorens, X., Mertsola, J., et al. Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. J Exp Med 1990; 172: 497–507.CrossRefGoogle ScholarPubMed
101.Saukkonen, K., Sande, S., Cioffe, C., et al. The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. J Exp Med 1990; 171: 439–448.CrossRefGoogle Scholar
102.Rhodes, RH.Evidence of serum-protein leakage across the bloodbrain barrier in the acquired immunodeficiency syndrome. J Neuropathol Exp Neurol 1991; 50: 171–183.CrossRefGoogle ScholarPubMed
103.Petito, CK., Cash, KS.Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol 1992; 32: 658–666.CrossRefGoogle ScholarPubMed
104.McArthur, JC., Nance-Sproson TE, Griffin, DE., et al. The diagnostic utility of elevation in cerebrospinal fluid beta 2-microglobulin in HIV-1 dementia. Multicenter AIDS Cohort Study. Neurology 1992; 42: 1707–1712.CrossRefGoogle ScholarPubMed
105.Smith, TW., DeGirolami, U., Henin, D., Bolgert, F., Hauw, JJ.Human immunodeficiency virus (HIV) leukoencephalopathy and the microcirculation. J Neuropathol Exp Neurol 1990; 49: 357–370.CrossRefGoogle ScholarPubMed
106.Adams, DH., Shaw, S.Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet 1994; 343: 831–836.CrossRefGoogle ScholarPubMed
107.Power, C., Kong, PA., McArthur, JC., et al. Alterations in the bloodbrain barrier associated with HIV dementia. Clin Neuropathol 1993; 3: 56.Google Scholar
108.Dow, SW., Poss, ML., Hoover, EA.Feline immunodeficiency virus: a neurotropic lentivirus. J Acquir Immune Defic Syndr 1990; 3: 658–668.Google ScholarPubMed
109.Tyor, WR., Power, C., Gendelman, HE., Markham, RB.A model of human immunodeficiency virus encephalitis in scid mice. Proc Natl Acad Sci USA 1993; 90: 8658–8662.CrossRefGoogle Scholar
110.Corboy, JR., Buzy, JM., Zink, MC., Clements, JE.Expression directed from HIV long terminal repeats in the central nervous system of transgenic mice. Science 1992; 258: 1804–1808.CrossRefGoogle ScholarPubMed
111.Toggas, SM., Masliah, E., Rockenstein, EM., et al. Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature 1994; 367: 188–193.CrossRefGoogle ScholarPubMed
112.Buller, RS., Wehrly, K., Portis, JL., Chesebro, B.Host genes conferring resistance to a central nervous system disease induced by a polytropic recombinant Friend murine retrovirus. J Virol 1990; 64: 493–498.CrossRefGoogle ScholarPubMed
113.Chesebro, B., Miyazawa, M., Britt, WJ.Host genetic control of spontaneous and induced immunity to Friend murine retrovirus infection. Ann Rev Immunol 1990; 8: 477–499.CrossRefGoogle ScholarPubMed
114.Rassart, E., Nelbach, L., Jolicoeur, P.Cas BrE murine leukemia virus: sequencing of the paralytogenic region of its genome and derivation of specific probes to study its origin and the structure of its recombinant genomes in leukemic tissues. J Virol 1986; 60: 910–919.CrossRefGoogle Scholar