Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Human immunodeficiency virus (HIV) envelope and core proteins in CNS tissues of patients with the acquired immune deficiency syndrome (AIDS)

Summary

Frequency, cellular tropism and relation to pathology of productive infection with human immunodeficiency virus (HIV) in human central nervous system (CNS) were studied. Serial sections of formolfixed and paraffin-embedded CNS tissues from 70 patients (69 with acquired immune deficiency syndrome, AIDS) were immunolabeled with monoclonal antibodies against HIV antigens (Ags) p17, p24, and gp41. Additional and double (immuno)stains were used to identify cell types and opportunistic infectious agents. HIV Ags were detected in 52 cases; they were restricted to cells with characteristics of microglia or macrophages. Anti-gp41, anti-p24, and anti-p17 labeled 50, 33, and 15 cases, respectively. Immunoreactivity for core proteins predominated in mature macrophages and microglia of fully developed lesions; additional immunoreactivity for gp41 was seen in microglia adjacent to, or unassociated with, histopathological lesions. Multifocal and/or diffuse lesions previously suggested as HIV induced because of characteristic histopathology, consistently contained large numbers of cells with HIV Ags (33 cases), confirming their HIV specificity. Isolated labeled microglia without associated pathology, found in seven brains, presumably represent the earliest stage of productive CNS infection by HIV. Lesions of opportunistic infections contained no (34 cases), few (16 cases), or many (4 cases) cells with HIV Ags. These data do not suggest transactivation of local HIV production by opportunistic agents as a frequent event in vivo. Development of specific HIV histopathology appears correlated with the number of productively infected cells.

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

References

  1. 1.

    Anand R, Thayer R, Srinivasan A, Nayyar S, Gardner M, Luciw P, Dandekar S (1989) Biological and molecular characterization of human immunodeficiency virus (HIV-1BR) from the brain of a patient with progressive dementia. Virology 168:79–89

  2. 2.

    Artigas J, Freund K, Grosse G, Niedobitek F (1989) Immunhistochemische Darstellung von HIV-p24-Antigen in formalin-fixiertem und paraffineingebettetem Hirn- und Rückenmarksgewebe. Pathologe 10:61–63

  3. 3.

    Budke H (1986) Multinucleated giant cells in brain: a hall-mark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 69:253–258

  4. 4.

    Budka H (1988) Pathogenesis of human immunodeficiency virus (HIV)-associated brain lesions: a neuropathological evaluation. Ann NY Acad Sci 540:630–633

  5. 5.

    Budka H (1989) Human immunodeficiency virus (HIV)-induced disease of the central nervous system: pathology and implications for pathogenesis. Acta Neuropathol 77: 225–236

  6. 6.

    Budka H (1989) CNS distribution of human immunodeficiency virus (HIV) antigens in AIDS. J Neuropathol Exp Neurol 48:384 [abstr]

  7. 7.

    Budka H (1990) Neuropathology of AIDS. In: Proc XIVth World Congr Neurol, Internat Congr Ser No 883. Elsevier, Amsterdam (in press)

  8. 8.

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

  9. 9.

    Budka H, Maier H, Pohl P (1988) Human immunodeficiency virus in vacuolar myelopathy of the acquired immunodeficiency syndrome. N Engl J Med 319:1667–1668

  10. 10.

    Cartun RW (1989) A sensitive immunocytochemical procedure for detecting HIV p24 core protein in formalin-fixed, paraffin-embedded tissues. DuPont Biotech Update 24: 18–19

  11. 11.

    Cartun RW, Knibbs DR, Pedersen CA, Cole SR, Berman MM (1988) Immunocytochemical localization of HIV in formalin-fixed tissues utilizing commercially available mAbs. Lab Invest 58:16A [abstr]

  12. 12.

    Cullen BR, Greene WC (1989) Regulatory pathways governing HIV-1 replication. Cell 58:423–426

  13. 13.

    Gabuzda DH, Ho DD, de la Monte SM, Hirsch MS, Rota TR, Sobel RA (1986) Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS. Ann Neurol 20:289–295

  14. 14.

    Griffin GE, Leung K, Folks TM, Kunkel S, Nabel GJ (1989) Activation of HIV gene expression during monocyte differentiation by induction of NF-kB. Nature 339:70–73

  15. 15.

    Györkey F, Melnick JL, Györkey P (1987) Human immunodeficiency virus in brain biopsies of patients with AIDS and progressive encephalopathy. J Infect Dis 155: 870–876

  16. 16.

    Hénin D, Duyckaerts C, Chaunu M-P, Vazeux R, Brousse N, Rozenbaum W, Hauw J-J (1987) Etude neuropathologique de 31 cas de syndrome d'immuno-dépression acquise. Rev Neurol (Paris) 143:631–642

  17. 17.

    Johnson RT, McArthur JC, Narayan O (1988) The neurobiology of human immunodeficiency virus infections. FASEB J 2:2970–2981

  18. 18.

    Kleihues P, Lang W, Burger PC, Budka H, Vogt M, Maurer R, Lüthy R, Siegenthaler W (1985) Progressive diffuse leukoencephalophathy in patients with acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 68: 333–339

  19. 19.

    Lyman WD, Kress Y, Rashbaum WK, Calvelli TA, Steinhauer E, Kashkin JM, Henderson CE, Rubinstein A (1988) An AIDS virus-associated antigen localized in human fetal brain. Ann NY Acad Sci 540:628–629

  20. 20.

    Maier H, Budka H, Lassmann H, Pohl P (1989) Vacuolar myelopathy with multinucleated giant cells in the acquired immune deficiency syndrome (AIDS). Light and electron microscopic distribution of human immunodeficiency virus (HIV) antigens. Acta Neuropathol 78:497–503

  21. 21.

    Manak M (1989) Histochemical detection of HIV-1 infected cells and tissues. DuPont Biotech Update 4:8–9

  22. 22.

    Michaels J, Price RW, Rosenblum MK (1988) Microglia in the giant cells encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion. Acta Neuropathol 76:373–379

  23. 23.

    Michaels J, Sharer LR, Epstein LG (1988) Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review. Immunodefic Rev 1:71–104

  24. 24.

    Nelson JA, Reynolds-Kohler C, Oldstone MBA, Wiley CA (1988) HIV and HCMV coinfect brain cells in patients with AIDS. Virology 165:286–290

  25. 25.

    Niederman TMJ, Thielan BJ, Ratner L (1989) Human immunodeficiency virus type 1 negative factor is a transcriptional silencer. Proc Natl Acad Sci USA 86:1128–1132

  26. 26.

    Petito CK, Navia BA, Cho ES, Jordan BD, George DC, Price RW (1985) Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N Engl J Med 312:874–879

  27. 27.

    Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–592

  28. 28.

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

  29. 29.

    Rhodes RH, Ward JM (1989) Immunohistochemistry of human immunodeficiency virus in the central nervous system and a hypothesis concerning the pathogenesis of AIDS meningoencephalomyelitis. In: Rotterdam H, Sommers SC, Racz P, Meyer PR (eds) Progress in AIDS pathology, vol 1. Field & Wood, Philadelphia, pp 167–179

  30. 30.

    Rhodes RH, Ward JM, Walker DL, Ross AA (1988) Progressive multifocal leukoencephalopathy and retroviral encephalitis in acquired immunodeficiency syndrome. Arch Pathol Lab Med 112:1207–1213

  31. 31.

    Rhodes RH, Ward JM, Cowan RP, Moore PT (1989) Immunohistochemical localization of human immunodeficiency viral antigens in formalin-fixed spinal cords with AIDS myelopathy. Clin Neuropathol 8:22–27

  32. 32.

    Schmidbauer M, Budka H (1989) Progressive multifocal leukoencephalopathy (PML) in AIDS and in the pre-AIDS era: a neuropathological comparison using immunocytochemistry and in situ hybridization. Clin Neuropathol 8:212–213 [abstr]

  33. 33.

    Schmidbauer M, Budka H, Okeda R, Cristina S, Costanzi G, Lechi A, Trabattoni GR (1989) Multifocal vacuolar leukoencephalopathy: a new type of HIV-induced neuropathology. Clin Neuropathol 8:249 [abstr]

  34. 34.

    Schmidbauer M, Budka H, Ambros P (1989) Herpes simplex virus (HSV) DNA in microglial nodular brainstem encephalitis. J Neuropathol Exp Neurol 48:645–652

  35. 35.

    Schmidbauer M, Budka H, Ulrich W, Ambros P (1989) Cytomegalovirus (CMV) disease of the brain in AIDS and connatal infection: a comparative study by histology, immunocytochemistry, and in situ DNA hybridization. Acta Neuropathol 79:286–293

  36. 36.

    Tersmette M, Gruters RA, Wolf F de, Goede REY de, Lange JMA, Schellekens PTA, Goudsmit J, Huisman HG, Miedema F (1989) Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol 63:2118–2125

  37. 37.

    Vass K, Lassmann H, Wekerle H, Wisniewski HM (1986) The distribution of Ia antigen in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 70:149–160

  38. 38.

    Vazeux R, Brousse N, Jarry A, Hénin D, Marche C, Vedrenne C, Mikol J, Wolff M, Michon C, Rozenbaum W, Bureau J-F, Montagnier L, Brahic M (1987) AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol 126:403–410

  39. 39.

    Ward JM, O'Leary TJ, Baskin GB, Benveniste R, Harris CA, Nara PL, Rhodes RH (1987) Immunohistochemical localization of human and simian immunodeficiency viral antigens in fixed tissue sections. Am J Pathol 127:199–205

  40. 40.

    Wiley CA, Nelson JA (1988) Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis. Am J Pathol 133:73–81

  41. 41.

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

  42. 42.

    Wiley CA, Grafe M, Kennedy C, Nelson JA (1988) Human immunodeficiency virus (HIV) and JC virus in acquired immune deficiency syndrome (AIDS) patients with progressive multifocal leukoencephalopathy. Acta Neuropathol 76:338–346

Download references

Author information

Additional information

Supported by the Austrian Fund for the Advancement of Scientific Research (P 7154-MED). Major parts of this study were presented at the Vth International Conference on AIDS, June 4–9, 1989, in Montreal, Canada (Th. B. P. 248)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Budka, H. Human immunodeficiency virus (HIV) envelope and core proteins in CNS tissues of patients with the acquired immune deficiency syndrome (AIDS). Acta Neuropathol 79, 611–619 (1990). https://doi.org/10.1007/BF00294238

Download citation

Key words

  • Acquired immune deficiency syndrome (AIDS)
  • Human immunodeficiency virus (HIV)
  • Immunocytochemistry
  • Macrophage
  • Microglia