Neurological Aspects of Human Immunodeficiency Virus Infection

  • Howard E. Gendelman
  • Seymour Gendelman
Part of the Infectious Agents and Pathogenesis book series (IAPA)


The human immunodeficiency virus (HIV), the etiologic agent of the acquired immune deficiency syndrome (AIDS),1–3 belongs to a taxonomic group of nononcogenic retroviruses termed lentivirinae that share biological, biochemical, and molecular features for viral persistence.4–11 The hallmark of HIV infection is a relentless and profound immunosuppression mediated by a selective depletion of helper/inducer T lymphocytes.12–15 However, the virus-infected macrophage is also intimately involved in HIV pathogenesis. Primary HIV-induced disease revolves around a near-exclusive replication of virus in multinucleated and mono-nucleated macrophages typified by central nervous system (CNS) infection.16-24 Brain macrophages are likely infected soon after viral exposure22–25 and contribute to CNS-related neuronal injury through the secretion of neurotoxins (of viral or cellular origin) and/or by coexistent opportunistic infections. Indeed, the highest levels of HIV gene expression found in brain macrophages are associated with clinical disease in infected individuals.25 The mechanisms by which HIV infection results in immunosuppression and progressive neurological disease are the primary focus of this chapter.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Human Immunodeficiency Virus Infection Acquire Immune Deficiency Syndrome Aseptic Meningitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Barre-Sinoussi, E, Chermann, J. C., Rey, E, Nugeryre, M. T., Chamaret, S., Gruest, J., Dauget, C., Axler-Blin, C., Vezinet-Brun, E, Rouzioux, C., Rosenbaum, W, and Montagnier, L., 1983, Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS), Science 220: 868–871.PubMedGoogle Scholar
  2. 2.
    Popovic, M., Sarngadharan, M. G., Read, E., and Gallo, R. C., 1984, Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS, Science 224: 497–500.PubMedGoogle Scholar
  3. 3.
    Levy, J. A., Hoffman, A. D., Kramer, S. M., Landis, J. A., Shimabukuro, J. M., and Oshiro, L. S., 1984, Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS, Science 225: 840–842.PubMedGoogle Scholar
  4. 4.
    Gonda, M. A., Wong-Staal, E, Gallo, R. C., Clements, J. E., Narayan, O., and Gilden, R. V, 1985, Sequence homology and morphologic similarity of HTLV III and visna virus, a pathogenic lentivirus, Science 227: 173–177.PubMedGoogle Scholar
  5. 5.
    Chiu, I. M., Yaniv, A., and Dahlberg, J. E., 1985, Nucleotide sequence evidence for relationship of AIDS retrovirus to lentiviruses, Nature 317: 366–368.PubMedGoogle Scholar
  6. 6.
    Rabson, A. B., and Martin, M. A., 1985, Molecular organization of the AIDS retrovirus, Cell 40: 477–480.PubMedGoogle Scholar
  7. 7.
    Guyader, M., Emerman, M., Sonigo, P., Clavel, E, Montagnier, L., and Alizon, M., 1987, Genome organization and transactivation of the human immunodeficiency virus, type 2, Nature 326: 662–669.PubMedGoogle Scholar
  8. 8.
    Narayan, O., and Cork, L. C., 1985, Lentiviral diseases of sheep and goats: Chronic pneumonia leukoencephalomyelitis and arthritis, Rev. Infect. Dis. 7: 89–98.PubMedGoogle Scholar
  9. 9.
    Haase, A. T., 1986, Pathogenesis of lentivirus infections, Nature 322: 130–136.PubMedGoogle Scholar
  10. 10.
    Narayan, O., 1990, Lentiviruses are etiological agents of chronic diseases in animals and acquired immunodeficiency syndrome in humans. Can. j Vet. Res. 54: 42–48.PubMedGoogle Scholar
  11. 11.
    Narayan, O., and Clements, J. E., 1989, Biology and pathogenesis of lentirviruses, J. Gen. Virol. 70: 1617–1639.PubMedGoogle Scholar
  12. 12.
    Gottlieb, M. S., Schroff, R., Schanker, H.M., Weisman, J. D., Fan, P. T., Wolf, R. A., and Saxon, A., 1981, Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: Evidence of a new acquired cellular immunodeficiency, N. Engl. J. Med. 305: 1425–1431.PubMedGoogle Scholar
  13. 13.
    Bowen, D. L., Lane, H. C., and Fauci, A. S., 1985, Immunopathogenesis of the acquired immunodeficiency syndrome, Ann. Intern. Med. 103: 704–709.PubMedGoogle Scholar
  14. 14.
    Popovic, M., Read-Connole, E., and Gartner, S., 1986, Biological properties of HTLV-III/ LAV: A possible pathway of natural infection in vivo, Ann. Inst. Pasteur. Immunol. 137D: 413–417.Google Scholar
  15. 15.
    Fauci, A. S., 1988, The human immunodeficiency virus: Infectivity and mechanisms of pathogenesis, Science 239: 617–622.PubMedGoogle Scholar
  16. 16.
    Gartner, S., Markovits, P., Markovitz, D. M., Kaplan, M. H., Gallo, R. C., and Popovic, M., 1986, The role of mononuclear phagocytes in HTLV-III/LAV infection, Science 233: 215–219.PubMedGoogle Scholar
  17. 17.
    Koenig, S., Gendelman, H. E., Orenstein, J. M., Dal Canto, M. C., Pezeshkpour, G. M., Yungbluth, M., Janotta, F., Aksamit, A., Martin, M. A., and Fauci, A. S., 1986, Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy, Science 233: 1089–1093.PubMedGoogle Scholar
  18. 18.
    Tschacler, E., Groh, V, Popovic, M., Mann, D. L., Konrad, K., Safai, B., Eron, L., diMarzo Veronese, E, Wolff, K., and Stingl, G., 1987, Epidermal Langerhans cells-a target for HTLV-III/LAV infection, J. Invest. Dermatol. 88: 233–237.Google Scholar
  19. 19.
    Salahuddin, S. Z., Rose, R. M., Groopman, J. E., Markham, P. D., and Gallo, R. C., 1986, Human T lymphotropic virus type III infection of human alveolar macrophages, Blood 68: 281–284.PubMedGoogle Scholar
  20. 20.
    Gendelman, H. E., Orenstein, J. M., Martin, M. A., Ferrua, C., Mitra, R., Phippa, T., Wahl, L. M., Lane, H. C., Fauci, A. S., Burke, D. S., Skillman, D., and Meltzer, M. S., 1988, Efficient isolation and propagation of human immunodeficiency virus on CSF 1 stimulated human monocytes, J Exp. Med. 167: 1428–1441.PubMedGoogle Scholar
  21. 21.
    Eilbott, D. J., Peress, N., Burger, H., LaNeve, D., Orenstein, J., Gendelman, H. E., Seidman, R,. and Weiser, B., 1989, Human immunodeficiency virus expression and replication in macrophages in the spinal cords of AIDS patients with myelopathy, Proc. Natl. Acad. Sci. U.S.A. 86: 3337–3341.PubMedGoogle Scholar
  22. 22.
    Gendelman, H. E., Orenstein, J. M., Baca, L. M., Weiser, B., Burger, H., Kalter, D. C., and Meltzer, M. S., 1989, Editorial review: The macrophage in the persistence and pathogenesis of HIV infection, AIDS 3: 475–495.PubMedGoogle Scholar
  23. 23.
    Schuitemaker, H., Kootstra, N. A., Goede, R. E. Y., De Wolf, E, Miedema, E, and Termette, M., 1991, Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants detectable in all stages of HIV-1 infection lack T-cell line tropism and syncytium-inducing ability in primary T-cell culture, J. Virol. 65: 356–363.PubMedGoogle Scholar
  24. 24.
    McElrath, M. J., Steinman, R. M., and Cohn, A. Z., 1991, Latent HIV-1 infection in enriched populations of blood monocytes and T cells from seropositive patients, J. Clin. Invest. 87: 27–30.PubMedGoogle Scholar
  25. 25.
    Price, R. W, Brew, B., Sidtis, J. Rosenblum, M., Scheck, A. C., and Cleary, P., 1988, The brain in AIDS: Central nervous system HIV-1 infection and AIDS dementia complex, Science 239: 586–592.PubMedGoogle Scholar
  26. 26.
    Cheevers, W. P., and McGuire, T. C., 1985, Equine infectious anemia virus: Immunopathogenesis and persistence, Rev. Infect. Dis. 7: 83–88.PubMedGoogle Scholar
  27. 27.
    Daniel, M. D., Letvin, N. L., King, N.W., Kannagi, M., Sehgal, P. K., Hunt, R. D., Kanki, P. J., Essex, M., and Desrosiers, R. C.,1985, Isolation of T-cell tropic HTLV III-like retrovirus from macaques, Science 228: 1201–1204.Google Scholar
  28. 28.
    Kanki, P. J., McLane, M. E, King, N. W., Jr., Letvin, N. L., Hunt, R. D., Sehgal, P., Daniel, M. D., Desrosiers, R. C., and Essex, M., 1985, Serologic identification and characterization of a macaque T-lymphotropic retrovirus closely related to HTLV III, Science 228: 1199–201.PubMedGoogle Scholar
  29. 29.
    Letvin, N. L., Daniel, M. D., Sehgal, P. K., Desrosiers, R. C., Hunt, R. D., Waldorn, L. M., Mackey, J. J., Schmidt, D. K., Chalifaux, L. V., and King, N. W, 1985, Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV III, Science 230: 71–73.PubMedGoogle Scholar
  30. 30.
    Pederson, N. C., Ho, E. W, Brown, M. L., and Yamamoto, J. K., 1987, Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome, Science 235: 790–793.Google Scholar
  31. 31.
    Sonigo, P., Alizon, M., Staskus, K., Klatzmann, D., Cole, S., Danos, O., Retzel, E., Tiollois, P., Haase, A., and Wain-Hobson, S., 1985 Nucleotide sequence of the visna lentivirus: Relationship to the AIDS virus, Cell 42: 369–382.PubMedGoogle Scholar
  32. 32.
    Stephens, R. M., Casey, J. W, and Rice, N. R., 1986, Equine infectious anemia virus gag and poi genes: Relatedness to visna and AIDS virus, Science 231: 589–594.PubMedGoogle Scholar
  33. 33.
    Harper, M. E., Marselle, L. M., Gallo, R. C., and Wong-Staal, E, 1986, Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization, Proc. Natl. Acad. Sci. U.S.A. 83: 772–776.PubMedGoogle Scholar
  34. 34.
    Narayan, O., Kennedy-Stoskopf, S., and Zink, C. M., 1988, Lentivirus-host interactions: Lessons from visna and caprine arthritis-encephalitis viruses, Ann. Neurol. 23 (Suppl.): 95–100.Google Scholar
  35. 35.
    Gendelman, H. E., Leonard, J. M., Dutko, E. J., Koenig, S., Khillan, J. S., and Meltzer, M. S., 1988, Immunopathogenesis of human immunodeficiency virus infection in the central nervous system, Ann. Neurol. 23 (Suppl.): S78–581.PubMedGoogle Scholar
  36. 36.
    Clements, J. E., Pedersen, E S., Narayan, O., and Haseltine, W. A., 1980, Genomic changes associated with antigenic variation of visna virus during persistent infection, Proc. Natl. Acad. Sci. U.S.A. 77: 4454 4458.Google Scholar
  37. 37.
    Narayan, O., Clements, J. E., Kennedy-Stoskopf, S., and Royal, R., 1987, Mechanisms of escape of visna lentiviruses from immunological control, Contrib. Microbiol. Immunol. 8: 60–76.PubMedGoogle Scholar
  38. 38.
    Kennedy-Stoskopf, S., and Narayan, O., 1986, Neutralizing antibodies to visna lentivirus: Mechanism of action and possible role in virus persistence, J. Virol. 59: 37–44.PubMedGoogle Scholar
  39. 39.
    Francis, D. P., and Petricciani, J. C., 1985, The prospects for and pathways toward a vaccine for AIDS, N. Engl. J. Med. 313: 1586–1590.PubMedGoogle Scholar
  40. 40.
    Hahn, B. H., Shaw, G. M., Taylor, M. E., Redfield, R. R., Markham, P. D., Salahuddin, S. Z., Wong-Staal, E, Gallo, R. G., Parks, E. S., and Parks, W. P., 1986, Genetic variation in HTLVIII-LAV over time in patients with AIDS or at risk for AIDS, Science 232: 1548–1553.PubMedGoogle Scholar
  41. 41.
    Ho, D. D., Sarnagaharan, M. G., Hirsch, M. S., Schooley, R. T., Rota, T. R., Kennedy, R. C., Chanh, T. C., and Sato, V. L., 1987, Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins, J Virol. 61: 2024–2028.PubMedGoogle Scholar
  42. 42.
    Bouillant, A. M. P., and Becker, S. A. W, 1984, Ultrastructural comparison of oncovirinae (type C), spumavirinae, and lentivirinae: Three subfamilies of retroviridae found in farm animals, J. Natl. Cancer Inst. 72: 1075–1084.PubMedGoogle Scholar
  43. 43.
    Dahlberg, J. E., Gaskin, J. M., and Perk, K., 1981, Morphological and immunological comparison of caprine arthritis encephalitis and ovine progressive pneumonia viruses, J Virol. 39: 914–919.PubMedGoogle Scholar
  44. 44.
    Gonda, M. A., Charman, H. P., Walker, J. L., and Coggins, L., 1978, Scanning and transmission electron microscopic study of equine infectious anemia virus, Am. j Vet. Res. 39: 731–740.PubMedGoogle Scholar
  45. 45.
    Munn, R. J., Marx, P. A., Yamamoto, J. K., and Gardner, M. B., 1985, Ultrastructural comparison of the retroviruses associated with human and simian acquired immunodeficiency syndromes, Lab. Invest. 53: 194–199.PubMedGoogle Scholar
  46. 46.
    Wain-Hobson, S., Sonigo, P., Danos, O., Cole, S., and Alizon, M., 1985, Nucleotide sequence of the AIDS virus, LAV, Cell 40: 9–17.PubMedGoogle Scholar
  47. 47.
    Ratner, L., Haseltine, W, Patarca, R., Livak, K. J., Starcich, B., Jacobs, S. E, Doran, E. R., Rafalski, J. A., Whitehorn, E. A., Baumeister, K., Ivanoff, L., Petteway, S. R., Pearson, M. L., Lautenberger, J. A., Papis, T. S., Ghrayeb, J., Chang, N. T., Gallo, R. C., and Wong-Staal, E, 1985, Complete nucleotide sequence of the AIDS virus, HTLV-III, Nature 313: 277–284.PubMedGoogle Scholar
  48. 48.
    Starcich, B., Ratner, L., Josephs, S. E, Okamoto, T, Gallo, R. C., and Wong-Staal, E, 1985, Characterization of long terminal repeat sequences of HTLV-III, Science 227: 538–540.PubMedGoogle Scholar
  49. 49.
    Muesing, M. A., Smith, D. H., Cabradilla, C. D., Benton, C. V., Lasky, L. A., and Capon, D. J., 1985, Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus, Nature 313: 450–458.PubMedGoogle Scholar
  50. 50.
    Sanchez-Pescador, R., Power, M. D., Barr, P. J., Steimer, K. S., Stemfeien, M. M., BrownShimer, S. L., Gee, W. W, Bernard, A., Randolph, A., Levy, J. A., Dina, D., and Luciw, P. A., 1985, Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2), Science 227. 484–492.PubMedGoogle Scholar
  51. 51.
    Schnittman, S. M., Psallidopoulos, M. C., Lane, H.O., Thompson, L., Baseler, M., Massari, E, Fox, C. H., Salzman, N. P., and Fauci, A. S., 1989, The reservoir for HIV-1 in peripheral blood is a T cell that maintains expression of CD4, Science 245: 305–308.PubMedGoogle Scholar
  52. 52.
    Ho, D. D., Moudgil, T., and Alam, M., 1989, Quantitation of human immunodeficiency virus type 1 in the blood of infected persons, N. Engl. J. Med. 321: 1621–1625.PubMedGoogle Scholar
  53. 53.
    Varmus, H., 1988, Retroviruses, Science 240: 1427–1435.PubMedGoogle Scholar
  54. 54.
    Weller, S. K., Joy, A. E., and Temin, H. M., 1980, Correlation between cell killing and massive second-round superinfection by members of some subgroups of avian leukosis virus, J. Virol. 33: 494–506.PubMedGoogle Scholar
  55. 55.
    Keshet, E., and Temin, H. M., 1979, Cell killing by spleen necrosis virus is correlated with a transient accumulation of spleen necrosis virus DNA, J. Virol. 31: 376–388.PubMedGoogle Scholar
  56. 56.
    Zagury, D., Bernard, J., Leonard, R., Cheynier, R., Feldman, M., Sarin, P. S., and Gallo, R. C., 1986, Long-term cultures of HTLVIII-infected T cells: a model of cytopathology of T-cell depletion in AIDS, Science 231: 850–853.PubMedGoogle Scholar
  57. 57.
    Klatzmann, D., and Gluckman, J. C., 1986, HIV infection: Facts and hypotheses, Immunol. Today 7: 291–296.Google Scholar
  58. 58.
    Maddon, P. J., Dalgleish, A. G., McDougal, J. S., Clapham, P. R., Weiss, R. A., and Axel, R., 1986, The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain, Cell 47: 333–348.PubMedGoogle Scholar
  59. 59.
    McDougal, J. S., Kennedy, M. S., Sligh, J. M., Cort, S. P., Mawle, A., and Nicholson, J. K. A., 1986, Binding of HTLVIII/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule, Science 231: 382–385.PubMedGoogle Scholar
  60. 60.
    Dalgleish, A. G., Beverley, P. C. L., Clapham, P.R., Crawford, D. H., Greaves, M. E, and Weiss, R. A., 1984, The CD4(T4) antigen is an essential component of the receptor for the AIDS retrovirus, Nature 312: 763–767.PubMedGoogle Scholar
  61. 61.
    Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guefard, D., Hersend, T., Gluckman, J-C., and Montagnier, L., 1984, T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV, Nature 312: 767–768.PubMedGoogle Scholar
  62. 62.
    McDougal, J. A., Mawle, A., Cort, S. R, Nicholson, J. K. A., Cross, G. D., SchepplerCampbell, J. A., Hicks, D., and Sligh, J., 1985, Role of T cell activation and expression of the T4 antigen, J. Immunol. 135: 3151–3162.PubMedGoogle Scholar
  63. 63.
    Ho, D. D., Pomerantz, R. J., and Kaplan, J. C., 1987, pathogenesis of infection with human immunodeficiency virus, N. Engl. J. Med. 317: 278–286.Google Scholar
  64. 64.
    DeRossi, A., Franchini, G., Aldonvini, A., del Mistro, A., Chieco-Bianchi, L., Gallo, R. C., and Wong-Staal, E, 1986, Differential response to the cytopathic effects of human T-cell lymphotropic virus type III (HTLV-III)-superinfection in T4+ (helper) and T8+ (suppressor) T-cell clones transformed by HTLV 1, Proc. Natl. Acad. Sci. U.S.A. 83: 4297–4301.Google Scholar
  65. 65.
    Ziegler, J. L., and Stites, D. R, 1986, Hypothesis: AIDS is an autoimmune disease directed at the immune system and triggered by a lymphotropic retrovirus, Clin. Immunol. Immunopathol. 41: 305–314.PubMedGoogle Scholar
  66. 66.
    Stricker, R. B., McHugh, T. M., Moody, D. J., Morrow, W. J. W, Stites, D. R, Shuman, M. A., and Levy, J. A., 1987, An AIDS-related cytotoxic autoantibody reacts with a specific antigen on stimulated CD4+ T cells, Nature 327: 710–713.PubMedGoogle Scholar
  67. 67.
    Schrier, R. D., Nelson, J. A., and Oldstone, M. B. A., 1985, Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection, Science 230: 1048.PubMedGoogle Scholar
  68. 68.
    Lane, H. C., Depper, J. M., Greene, W. C., Gail Whalen, B. S., Waldmann, T. A., and Fauci, A. S., 1985, Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome evidence for a selective defect in soluble lantigen recognition, N. Engl. J. Med. 313: 79–85.PubMedGoogle Scholar
  69. 69.
    Lane, H. C., Masur, H., Edgar, L. C., Whalen, G., Rook, A. H., and Fauci, A. S., 1983, Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome, N. Engl. J. Med. 309: 453–458.PubMedGoogle Scholar
  70. 70.
    Margolick, D. J., Volkman, D. J., Folks, T M., and Fauci, A. S.,1987, Amplification of HTLV III/LAV infection by antigen-induced activation of T cells and direct suppression by virus of lymphocyte blastogenic responses, J. Immunol. 138: 1719–1723.Google Scholar
  71. 71.
    Schnittman, S. M., Lane, H. C., Higgins, S. E., Folks, T, and Fauci, A. S., 1986, Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus, Science 233: 1083–1086.Google Scholar
  72. 72.
    Narayan, O., and Zink, C., 1987, Role of macrophages in lentivirus infections, in: Immunodeficiency Disorders and Retroviruses ( K. Perk, ed.), Academic Press, New York.Google Scholar
  73. 73.
    Orenstein, J. M., Meltzer, M. S., Phipps, T, and Gendelman, H. E., 1988, Cytoplasmic assemble and accumulation of human immunodeficiency virus types 1 and 2 in recombinant human colony-stimulating factor-l-treated human monocytes: An ultrastructural study, J. Virol. 62: 2578–2586.PubMedGoogle Scholar
  74. 74.
    Ringler, D. J., Hunt, R. D., Desrosiers, R. C., Daniel, M. D., Chalifoux, L. V., and King, N. W, 1988, Simian immunodeficiency virus-induced meningoencephalitis: Natural history and retrospective study, Ann. Neurol. 23: 101–107.Google Scholar
  75. 75.
    Gendelman, H. E., Narayan, O., Kennedy-Stoskopf, S., Kennedy, P. G. E., Ghotbi, Z., Clements, J. E., Stanley, J., and Pezeshkpour, G. H., 1986, Tropism of sheep lentiviruses for monocytes: Susceptibility to infection and virus gene expression increases during maturation of monocytes to macrophages, J. Virol. 58: 67–74.PubMedGoogle Scholar
  76. 76.
    Gendelman, H. E., Narayan, O., Molineaux, S., Clements, J. E., and Ghotbi, Z., 1985, Slow persistent replication of lentiviruses: Role of macrophages and macrophage precursors in bone marrow, Proc. Natl. Acad. Sci. U.S.A. 82: 7086–7090.PubMedGoogle Scholar
  77. 77.
    Gendelman, H. E., Narayan, O., Kennedy-Stoskopf, S., Clements, J. E., and Pezeshkpour, G. H 1984, Slow virus macrophage interactions: Characterization of a transformed cell line of sheep alveolar macrophages that express a marker for susceptibility to ovine–caprine lentivirus infections, Lab. Invest. 51: 547–555.PubMedGoogle Scholar
  78. 78.
    Stoler, M. H., Eskin, T. A., Benn, S., Angerer, R. C., and Angerer, L. M., 1986, Human T-cell lymphotropic virus type III infection of the central nervous system—a preliminary in situ analysis, J.A.M.A. 256: 2360–2364.PubMedGoogle Scholar
  79. 79.
    Wiley, C. A., Schrier, R. D., Nelson, J. A., Lampert, P. W, and Oldstone, M. B.A., 1986, Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients, Proc. Natl. Acad. Sci. U.S.A. 83: 7089–7093.PubMedGoogle Scholar
  80. 80.
    Vazeux, R., Brousse, N., Jarry, A., Henin, D., Marche, C., Vedrenne, C., Mikol, J., Wolff, M., Michon, C., Rozenbaum, W, Bureau, J.-E., Montagnier, L., and Brahic, M., 1987, AIDS subacute encephalitis; identification of HIV-infected cells, Am. J. Pathol. 126: 403–410.PubMedGoogle Scholar
  81. 81.
    Michaels, J., Sharer, L. R., and Epstein, L. G., 1988, Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review, Immunodef. Rev. 1: 71–104.PubMedGoogle Scholar
  82. 82.
    Gabuzda, D. H., Ho, D. D., de al Monte, S. M., Hirsch, M. S., Rota, T. R., and Sobel, R. A., 1986, Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS, Ann. Neurol. 20: 289–295.Google Scholar
  83. 83.
    Chayt, K. J., Harper, M. E., Marselle, L. M., Lewin, E. B., Rose, R. M., Oleske, J. M., Epstein, L. G., Wong-Staal, E, and Gallo, R. C., 1986, Detection of HTLV III RNA in lungs of patients with AIDS and pulmonary involvement, A.M.A. 256: 2356–2359.Google Scholar
  84. 84.
    Le Tourneau, A., Audouin, J., Diebold, J., Marche, C., Tricottet, V., and Reynes, M., 1986, LAY-like viral particles in lympho node germinal centers in patients with the persistent lymphadenopathy syndrome and the acquired immunodeficiency syndrome-related complex: An ultrastructural study of 30 cases, Hum. Pathol 17: 1047–1053.PubMedGoogle Scholar
  85. 85.
    Bender, B. S., Davidson, B. L., Kline, R., Brown, C., and Quinn, T., 1988, Role of the mononuclear phagocyte system in the immunopathogenesis of human immunodeficiency virus infection and the acquired immunodeficiency syndrome, Rev. Infect. Dis. 10: 1142–1154.PubMedGoogle Scholar
  86. 86.
    Navia, B. A., Jordan, B. D., and Price, R. W, 1986, The AIDS dementia complex: I. Clinical features, Ann. Neurol. 19: 517–524.PubMedGoogle Scholar
  87. 87.
    Navia, B. A., Cho, E.-S., Petito, C. K., and Price, R. W, 1986, The AIDS dementia complex: II. Neuropathology, Ann. Neurol. 19: 525–535.PubMedGoogle Scholar
  88. 88.
    de la Monte, S. M., Ho, D. D., Schooley, R. T., Hirsh, M. S., and Richardson Jr., E. P., 1987, Subacute encephalomyelitis of AIDS and its relation to HTLV-III infection, Neurology 37: 562–569.PubMedGoogle Scholar
  89. 89.
    Levy, R. M., Bredesen, D. E., and Rosenblum, M. L., 1988, Opportunistic central nervous system pathology in patients with AIDS, Ann. Neurol. 23 (Suppl.): S7 - S12.PubMedGoogle Scholar
  90. 90.
    Snider, W. D., Simpson, M. D., Nielsen, S., Gold, J. W. M., Metroka, C. E., and Posner, J. B., 1983, Neurological complications of acquired immune deficiency syndrome: Analysis of 50 patients, Ann. Neurol. 14: 403–418.PubMedGoogle Scholar
  91. 91.
    Bredesen, D. E., Lipkin, W. I., and Messing, R., 1983, Prolonged recurrent aseptic meningitis with prominent cranial nerve abnormalities: A new epidemic in gay men? Neurology 33 (Suppl.): 85.Google Scholar
  92. 92.
    Cooper, D. A., Gold, J., Maclean, P., Donovan, B., Finlayson, R., Barnes, T. G., Michelmore, H. M., Brooke, P., and Penny, R., 1985, Acute AIDS retrovirus infection: Definition of a clinical illness associated with seroconversion, Lancet 1: 537–540.PubMedGoogle Scholar
  93. 93.
    Hollander, H., and Stringari, S., 1987, Human immunodeficiency virus-associated meningitis: Clinical course and correlations, Am. J. Med. 83: 813–816.PubMedGoogle Scholar
  94. 94.
    Ho, D. D., Sarngadharan, M. G., Resnick, L., DiMarzo-Veronese, F., Rota, T. R., and Hirsch, M. S., 1985, Primary human T-lymphotropic virus type III infection, Ann. Intern. Med. 103: 880–883.PubMedGoogle Scholar
  95. 95.
    Griffin, D. E., McArthur, J. C., and Cornblath, D. R., 1991, Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV associated neurologic disease, Neurology 4: 69–74.Google Scholar
  96. 96.
    Bredesen, D. E., and Messing, R., 1983, Neurological syndromes heralding the acquired immune deficiency syndrome, Ann. Neurol. 14: 141.Google Scholar
  97. 97.
    McArthur, J. C., Cohen, B. A., Farzedegan, H., Cornblath, D. R., Seines, O. A., Ostrow, D., Johnson, R. T., Phair, J., and Polk, B. E, 1988, Cerebrospinal fluid abnormalities in homosexual men with and without neuropsychiatric findings, Ann. Neurol. 23 (Suppl.): S34 - S37.PubMedGoogle Scholar
  98. 98.
    Goudsmit, J., Wolters, E. C., Bakker, M., Smit, L., van der Noordaa, J., Hische, E. A. H., Tutuarima, J. A., and van der Helm, H. J., 1986, Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex, Br. Med. J. 292: 1231–1234.Google Scholar
  99. 99.
    Levy, J. A., Shimabukuro, J., Hollander, H., Mills, J., and Kaminsky, L., 1985, Isolation of AIDS-associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms, Lancet 2: 586–588.PubMedGoogle Scholar
  100. 100.
    Ho, D. D., Rota, T. R., Schooley, R. T., 1985, Isolation of HTLV-III from cerebrospinal fluid and neural tissue of patients with neurologic syndromes related to the acquired immunodeficiency syndrome, N. Engl. J. Med. 313: 1493–1497.PubMedGoogle Scholar
  101. 101.
    Levy, R. M., Bredesen, D. E., and Rosenblum, M. C., 1985, Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at UCSF and review of the literature, J Neurosurg. 62: 475–495.PubMedGoogle Scholar
  102. 102.
    Kieburtz, K., and Schiffer, R. B., 1989, Neurologic manifestations of human immunodeficiency virus infections, Neurol. Clin. 7: 447–468.PubMedGoogle Scholar
  103. 103.
    Price, R. W, Sidtis, J., and Rosenblum, M., 1988, The AIDS dementia complex: Some current questions, Ann. Neurol. 23 (Suppl.): S27 - S33.PubMedGoogle Scholar
  104. 104.
    Berger, J. R., Moskowitz, L., and Fishl, M., 1984, The neurologic complications of AIDS: Frequently the initial manifestation, Neurology 34 (Suppl. 1): 134–135.Google Scholar
  105. 105.
    Navia, B. A., and Price, R. W, 1987, The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection, Arch. Neurol. 44: 65–69.PubMedGoogle Scholar
  106. 106.
    Parisi, A., Strosselli, M., DiPerri, G., Silvano, C., Minoli, L., Bono, G., Moglia, A., and Nappi, G., 1989, Electroencephalography in the early diagnosis of HIV-related subacute encephalitis: analysis of 185 patients. Clin EEG 20: 1–5.Google Scholar
  107. 107.
    Gabuzda, D. H., Levy, S. R., and Chiappa, K. H., 1988, Electroencephalography in AIDS and AIDS-related complex, Clin Electroencephalogr. 19: 1–6.PubMedGoogle Scholar
  108. 108.
    Parisi, A., Stossell, M., Pan, A., Maserati, R., and Minoli, L., 1991, HIV-related encephalitis presenting as convulsant disease, Clin. Electroencephalogr. 22: 1–4.PubMedGoogle Scholar
  109. 109.
    Cummings, J. L., and Benson, D. E, 1984, Subcortical dementia-review of an emerging concept, Arch. Neurol. 41: 874–879.PubMedGoogle Scholar
  110. 110.
    Cummings, J. L., and Benson, E, 1983, Dementia: Definition, prevalence, classification, and approach to diagnosis, in: Dementia: A Clinical Approach, Butterworths, Stoneham, MA, pp. 7–10.Google Scholar
  111. 111.
    Fraser, M., 1987, Dementia: Its Nature and Management, Bath Press, Avon, Great Britain.Google Scholar
  112. 112.
    Nath, A., Jancovic, J., and Pettigrew, L. C., 1987, Movement disorders and AIDS, Neurology 37: 37–41.PubMedGoogle Scholar
  113. 113.
    Metzer, W. S., 1987, Movement disorders with AIDS encephalopathy: A case report, Neurology 37: 1438.PubMedGoogle Scholar
  114. 114.
    Gabuzda, D. H., and Hirsch, M. S., 1987, Neurologic manifestations of infection with human immunodeficiency virus. Clinical features and pathogenesis, Ann. Intern. Med. 107: 383–391.PubMedGoogle Scholar
  115. 115.
    Epstein, L. G., Sharer, L. R., and Goudsmit, J., 1988, Neurological and neuropathological features of human immunodeficiency virus infection in children, Ann. Neurol. 23 (Suppl.): S19 - S23.PubMedGoogle Scholar
  116. 116.
    Epstein, L. G., Sharer, L. R., Joshi, V. V., Fojas, M. M., Koenigsberger, M. R., and Oleske, J. M., 1985, Progressive encephalopathy in children with acquired immune deficiency syndrome, Ann. Neurol. 17: 488–496.PubMedGoogle Scholar
  117. 117.
    Iannetti, P., Falconieri, P., and Imperato, C., 1989, Acquired immune deficiency syndrome in childhood. Neurological aspects, Child. Nerv. Syst. 5: 281–287.Google Scholar
  118. 118.
    Pumarola-Sune, T, Navia, B. A., Cordon-Cardo, C., Cho, E.-S., and Price, R. W, 1987, HIV antigen in the brains of patients with the AIDS dementia complex, Ann. Neurol. 21: 490–496.PubMedGoogle Scholar
  119. 119.
    Grant, I., Atkinson, J. H., Hesselink, J. R., Kennedy, C. J., Richman, D. D., Spector, S. A., and McCutchan, J. A., 1987, Evidence for early CNS involvement in AIDS and other HIV infections, Ann. Intern. Med. 107: 828.PubMedGoogle Scholar
  120. 120.
    Saykin, A. J., Janssen, R. S., Sprehn, G. C., Kaplan, J. E., Spira, T. J., and Weller, P., 1984, Neuropsychological dysfunction in AIDS-related complex, Neurology 37 (Suppl. 1): 374.Google Scholar
  121. 121.
    Rubinow, D. R., Berrettini, C. H., Brouwwers, P., and Lane, H. C., 1988, Neuropsychiatric consequences of AIDS, Ann. Neurol. 23 (Suppl.): 524–26.Google Scholar
  122. 122.
    Yarchoan, R., Thomas, R. V., Grafman, J., Wichman, A., Dalakas, M., McAtee, N., Berg, G., Fishl, M., Perno, C. F., Klecker, R. W, Buchbinder, A., Tay, S., Larson, S. M., Myers, C. E., and Broder, S., 1988, Long-term administration of 3’-azido-2’,3’- dideoxythymidine to patients with AIDS-related neurological disease, Ann. Neurol. 23 (Suppl.): S82 - S87.PubMedGoogle Scholar
  123. 123.
    Johnson, V. A., and Hirsch, M. S., 1990. New developments in antiretroviral drug therapy for human immunodeficiency virus infections, in: AIDS Clinical Review 1990 ( P. Volberding and M. A. Jacobson, eds.), Marcel Dekker, New York, pp. 235–272.Google Scholar
  124. 124.
    Johnson, R. T, and McArthur, J. C., 1987, Myelopathies and retroviral infections, Ann. Neurol. 21: 113–116.PubMedGoogle Scholar
  125. 125.
    Griffin, J. W, McArthur, J. C., and Cornblath, D. R., 1990, Peripheral nerve and spinal cord disease in human retrovirus infections, Curr. Opin. Neurol. Neurosurg. 3: 697–703.Google Scholar
  126. 126.
    Petito, C. K., Navia, B. A., Cho, E.-S., and Jordan, B. D., 1985, Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with acquired immunodeficiency syndrome (AIDS), N. Engl. J. Med. 312: 874–879.PubMedGoogle Scholar
  127. 127.
    Sharer, L. R., Epstein, L. G., Cho, E. S., and Petito, C. D., 1986, HTLV-III and vacuolar myelopathy, N. Engl. J. Med. 315: 62–63.Google Scholar
  128. 128.
    Petito, C., 1988, Review of central nervous system pathology in human immunodeficiency virus infection, Ann. Neurol. 23 (Suppl.): S54 - S57.PubMedGoogle Scholar
  129. 129.
    Miller, R. G., Kiprov, D. D., Parry, G., and Bredesen, D. E., 1988, Peripheral nervous system dysfunction in acquired immunodeficiency syndrome, in: AIDS and the Nervous System ( M. L. Rosenblum, R. M. Levy, and D. E. Bredesen, eds.), Raven Press, New York, pp. 65–78.Google Scholar
  130. 130.
    Roman, G. C., 1987, Retrovirus associated myelopathies, Arch. Neurol. 44: 659–663.PubMedGoogle Scholar
  131. 131.
    Dalakas, M. C., and Pezeshkpour, G. H., 1988, Neuromuscular diseases associated with human immunodeficiency virus infection, Ann. Neurol. 23 (Suppl.): S38 - S48.PubMedGoogle Scholar
  132. 132.
    Lipkin, W. I., Parry, G., Kiprov, D., and Abrams, D., 1985, Inflammatory neuropathy in homosexual men with lymphadenopathy, Neurology 35: 1479–1483.PubMedGoogle Scholar
  133. 133.
    Eidelberg, D., Sotrel, A., Vogel, H., Walker, P., Kleefield, J., and Crumpacker III, C. S., 1986, Progressive polyradiculopathy in acquired immune deficiency syndrome, Neurology 36: 912–916.PubMedGoogle Scholar
  134. 134.
    So, Y. T., Holtzman, D. M., Abrams, M. I., and Olney, R. K., 1988, Peripheral neuropathy associated with acquired immunodeficiency syndrome, Arch. Neurol. 48: 945–948.Google Scholar
  135. 135.
    Cohen, J. A., and Laudenslager, M., 1989, Autonomic nervous system involvement in patients with human immunodeficiency virus infection, Neurology 39: 1111–1112.PubMedGoogle Scholar
  136. 136.
    Parry, G. J., 1988, Peripheral neuropathies associated with human immunodeficiency virus infection, Ann. Neurol. 23 (Suppl.): S49 - S53.PubMedGoogle Scholar
  137. 137.
    Gabbai, A. A., Schmidt, B., Costelo, A., Oliveira, A. S. B., and Lima, J. G. C., 1990, Muscle biopsy in AIDS and ARC: Analysis of 50 patients, Muscle Nerve 13: 541–544.PubMedGoogle Scholar
  138. 138.
    Cornblath, D. R., McArthur, J. C., and Griffin, J. W, 1986, The spectrum of peripheral neuropathies in HTLV-III infection, Muscle Nerve 9: 76.Google Scholar
  139. 139.
    Cornblath, D. R., McArthur, J. C., Kennedy, G. E., Witte, A. S., and Griffin, J. W, 1987, Inflammatory demyelinating peripheral neuropathies associated with human T-lymphotropic virus type III infection, Ann. Neurol. 21: 32–40.PubMedGoogle Scholar
  140. 140.
    Chaunu, M. P., Ratinahirana, H., Raphael, M., Henin, D., Leport, C., Brun-Vezinet, E, Leger, J.-M., Brunet, P., and Hauw, J.J., 1989, The spectrum of changes on 20 nerve biopsies in patients with HIV infection, Muscle Nerve 12: 451–459.Google Scholar
  141. 141.
    Vendrell, J., Heredia, C., Pujol, M., Asjo, B., and Fenyo, E. M., 1987, Guillain-Barré syndrome associated with seroconversion for anti-LAV/HTLV-III, Neurology 37: 544.PubMedGoogle Scholar
  142. 142.
    Rance, N. E., McArthur, J. C., Cornblath, D. R., Landstrom, D. L., Griffin, J. W., and Price, D. L., 1988, Gracile tract degeneration in patients with sensory neuropathy and AIDS, Neurology 38: 265–271.PubMedGoogle Scholar
  143. 143.
    Miller, R. G., Parry, G., Lang, W., Lippert, R., and Kiprov, D., 1985, AIDS-related inflammatory polyradiculoneuropathy: Prediction of response to plasma exchange with electrophysiologic testing, Muscle Nerve 8: 626.Google Scholar
  144. 144.
    Miller, R. G., Storey, J. R., and Greco, C. M., 1990, Ganciclovir in the treatment of progressive AIDS-related polyradiculopathy, Neurology 40: 569–574.PubMedGoogle Scholar
  145. 145.
    Dalakas, M. C., Pezeshkpour, G. H., Gravell, M., and Sever, J. L., 1986, Polymyositis associated with AIDS retrovirus, J.A.M.A. 256: 2381–2383.PubMedGoogle Scholar
  146. 146.
    Watkins, B. A., Dorn, H. H., Kelly, W. B., Armstrong, R. C, Potts, B., Michaels, E, Kufta, C. V., and Dubois-Dalcq, M., 1990, Specific tropism of HIV-1 for microglial cells in primary human brain cultures, Science 249: 549–553.PubMedGoogle Scholar
  147. 147.
    Chiodi, E, Fuerstenberg, S., Gidlund, M., Asjö, B., and Fenyö, E. M., 1987, Infection of brain-derived cells with the human immunodeficiency virus, J. Virol. 61: 1244–1247.PubMedGoogle Scholar
  148. 148.
    Popovic, M., Mellert, W, Erfle, V., and Gartner, S., 1988, Role of mononuclear phagocytes and accessory cells in human immunodeficiency virus type I infection of the brain, Ann. Neurol. 23 (Suppl.): 74–77.Google Scholar
  149. 149.
    Cheng-Mayer, C., Rutka, J. T., Rosenblum, M. L., McHugh, T., Stites, D. P., and Levy, J. A., 1987, Human immunodeficiency virus can productively infect cultured human glial cells, Proc. Natl. Acad. Sci. U.S.A. 84: 3526–3530.PubMedGoogle Scholar
  150. 150.
    Funke, I., Hahn, A., Rieber, E. P., Weiss, E., and Reithmuller, G., 1987, 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.PubMedGoogle Scholar
  151. 151.
    Gendelman, H. E., Phelps, W, Fiegenbaum, L., Adachi, A., Ostrove, J. M., Howley, P. M., Khoury, G., Ginsberg, H. S., and Martin, M. A., 1986, Transactivation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses, Proc. Natl. Acad. Sci. U.S.A. 83: 9759–9763.PubMedGoogle Scholar
  152. 152.
    Brenneman, D. E., Westbrook, G. L., Fitzgerald, S. P., Ennist, D. L., Elkins, K. L., Ruff, M. R., and Pert, C. B., 1989, Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide, Nature 335: 639–642.Google Scholar
  153. 153.
    Dreyer, E. B., Kaiser, P. K., Offermann, J. T., and Lipton, S. A., 1990, HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists, Science 248: 364–367.PubMedGoogle Scholar
  154. 154.
    Sabatier, J.-M., Vives, E., Mabrouk, K., Benjouad, A., Rochat, H., Duval, A., Hue, B., and Bahroui, E., 1991, Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1, J. Virol. 65: 961–967.PubMedGoogle Scholar
  155. 155.
    Serwadda, D., Mugerwa, R. D., Sewankambo, N., Lwegaba, A., Carswell, J. W, Kirya, G. B., Bayley, A. C., Downing, R. G., Tedder, R. S., Clayden, S. A., Weiss, R. A., and Dalgleish, A. G., 1985, Slim disease: A new disease in Uganda and its association with HTLV III infection, Lancet 2: 849–852.PubMedGoogle Scholar
  156. 156.
    Giulian, D., Vaca, K., and Noonan, C. A., 1991, Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1, Science 250: 1593–1596.Google Scholar
  157. 157.
    Bryant, H., Burgess, S., Gendelman, H. E., Meltzer, M. S., Holaday, J., and Berton, E., 1991, Neuronotropic activity associated with monocyte growth factors and products of stimulated monocytes, in: Peripheral Signalling of the Brain in Neuroimmune and Cognitive Function, ( R. C. A. Frederickson, ed.), Hogrefe and Huber, Toronto, pp. 83–99.Google Scholar
  158. 158.
    Belsito, D. V., Sanchez, M. R., Baer, R. L., Valentine, E, and Thorbecke, G. J., 1984, Reduced Langerhans’ cell la antigen and ATPase activity in patients with the acquired immunodeficiency syndrome, N. Engl. J. Med. 310: 1279–1282.PubMedGoogle Scholar
  159. 159.
    Kanitakis, J., Marchacd, C., Su, H., Thivolet, J., Zambruno, G., Schmitt, D., and Gazzolo, L., 1989, Immunohistochemical study of normal skin of HIV-1-infected patients shows no evidence of infection of epidermal Langerhans’ cells by HIV, AIDS Res. Hum. Retrovir. 5: 293–302.PubMedGoogle Scholar
  160. 160.
    Roy, S., and Wainberg, M. A., 1988, Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS), J. Leuk. Biol. 43: 91–97.Google Scholar
  161. 161.
    Pauza, C. D., 1988, HIV Persistence in monocytes leads to pathogenesis and AIDS, Cell. Immunol. 112: 414–419.PubMedGoogle Scholar
  162. 162.
    Nabel, G., and Baltimore, D., 1987, An inducible transcription factor activates expression of human immunodeficiency virus in T cells, Nature 326: 711–713.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1992

Authors and Affiliations

  • Howard E. Gendelman
    • 1
    • 2
  • Seymour Gendelman
    • 3
  1. 1.HIV-Immunopathogenesis Program, Department of Cellular ImmunologyWalter Reed Army Institute of ResearchRockvilleUSA
  2. 2.Henry M. Jackson Foundation for the Advancement of Military MedicineUniformed Services University Health Science CenterBethesdaUSA
  3. 3.Department of NeurologyMt. Sinai Medical CenterNew YorkUSA

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