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Human immunodeficiency virus (HIV) and JC virus in acquired immune deficiency syndrome (AIDS) patients with progressive multifocal leukoencephalopathy

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Summary

Of the 93 acquired immune deficiency syndrome (AIDS) patients autopsied between 1983 and 1986, 27 had evidence of viral encephalitis of which 3 had progressive multifocal leukoencephalopathy (PML), confirmed by electron microscopy. Using in situ hybridization with biotinylated JC virus probes, paraffin sections from the brains of these 27 patients were examined. JC virus was found only in those patients with histologically proven PML, while no evidence of JC virus was detected in the brains of the other 24 AIDS patients despite the presence of white matter pathology. Brain biopsies of the PML patients demonstrated human immunodeficiency virus (HIV)-infected macrophages infiltrating regions of demyelination. When the patients died (2 to 6 months after diagnosis of PML), many more macrophages contained HIV antigens and some had fused to form multinucleated giant cells. These findings suggest that in AIDS patients, papovaviruses not only cause damage by directly infecting oligodendroglia but causes additional damage by eliciting the ingress of macrophages latently infected with HIV. As was seen with other infections (e.g., cytomegalovirus) of the CNS this might be a general mechanism of HIV entry into the brain.

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References

  1. Aksamit AJ, Mourrain P, Sever JL, Major EO (1985) Progressive multifocal leukoencephalopathy: investigation of three cases using in situ hybridization with JC virus biotinylated DNA probe. Ann Neurol 18:490–496

    Google Scholar 

  2. Aksamit AJ, Sever JL, Major EO (1986) Progressive multifocal leukoencephalopathy: JC virus detection by in situ hybridization compared with immunohistochemistry. Neurology 36:499–504

    Google Scholar 

  3. Anders KH, Guerra WF, Tomiyasu U, Verity MA, Vinters HV (1986) The neuropathology of AIDS: UCLA experience and review. Am J Pathol 124:537–558

    Google Scholar 

  4. Astrom KE, Mancall EL, Richardson EP Jr (1958) Progressive multifocal leukoencephalopathy. Brain 81:794–797

    Google Scholar 

  5. Cavanagh JB, Greenbaum D, Marshall AHE, Rubinstein LJ (1959) Cerebral demyelination associated with disorders of the reticuloendothelial system. Lancet II:525–529

    Google Scholar 

  6. Folks T, Powell DM, Lightfoote MM, Benn S, Martin MA, Fauci AS (1986) Induction of HTLV-III/LAV from a nonvirus producing T-cell line: implications for latency. Science 231:600–602

    Google Scholar 

  7. Gartner S, Markovits P, Markovits DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 215:215–219

    Google Scholar 

  8. Gowen A, Tsukada T, Ross R (1986) Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions. Am J Pathol 125:91–207

    Google Scholar 

  9. Gray F, Gherardi R, Baudrimont M, Gaulard P, Meyrignac C, Vedrenne L, Poirier J (1987) Leukoencephalopathy with multinucleated giant cells containing human immune deficiency virus-like particles and multiple opportunistic infections in one patient with AIDS. Acta Neuropathol (Berl) 73:99–104

    Google Scholar 

  10. Gurney ME, Heinrich SP, Lee MR, Yin H-S (1986) Molecular cloning and expression of Neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science 234:566–574

    Google Scholar 

  11. Gurney ME, Apatoff BR, Spear GT, Baumel MJ, Antel JP, Brown M, Bania B, Reder AT (1986) Neuroleukin: a lymphokine product of lectin-stimulated T cells. Science 234:574–581

    Google Scholar 

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

    Google Scholar 

  13. Harris AA, Segreti J, Levin S (1985) Central nervous system infections in patients with acquired immune deficiency syndrome (AIDS). Clin Neuropharmacol 8:201–210

    Google Scholar 

  14. Hoxie JA, Haggarty BS, Rackowski JL, Pillsbury N, Levy JA (1985) Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. Science 229:1400–1402

    Google Scholar 

  15. Itoyama Y, Webster HdeF, Sternberger NH, Richardson EP Jr, Walker DL, Quarles RH, Padgett BL (1982) Distribution of papovavirus, myelin-associated glycoprotein, and myelin basic protein in progressive multifocal leukoencephalopathy lesions. Ann Neurol 11:396–407

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  18. Levy RM, Bredesen DE, Rosenblum ML (1985) Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg 62:475–495

    Google Scholar 

  19. Maddon PJ, Dalgleish AG, McDougal JS, Clapham PR, Weiss RA, 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

    Google Scholar 

  20. Moskowitz LB, Hensely GT, Chan JC, Gregorios J, Conley FK (1984) The neuropathology of acquired immune deficiency syndrome. Arch Pathol Lab Med 109:867–872

    Google Scholar 

  21. Narayan O, Cork LC (1985) Lentiviral diseases of sheep and goats: chronic pneumonia leukoencephalomyelitis and arthritis. Rev Infect Dis 7:89–98

    Google Scholar 

  22. Nielsen SL, Petito CK, Urmacher CD, Posner JB (1984) Subacute encephalitis in acquired immune deficiency syndrome: a postmortem study. Am J Clin Pathol 82:678–682

    Google Scholar 

  23. Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH (1971) Cultivation of papova-like virus from human brain with progressive multifocal leukoencephalopathy. Lancet I:1257–1260

    Google Scholar 

  24. Penney JB Jr, Weiner LP, Herndon RM, Narayan O, Johnson RT (1972) Virions from progressive multifocal leukoencencephalopathy: rapid serological identification by electron microscopy. Science 178:60–62

    Google Scholar 

  25. Shaw GM, Harper ME, Hahn BH, Epstein LG, Gajdusek DC, Price RW, Navia BA, Petito CK, O'Hara CJ, Cho E-S, Oleske JM, Wong-Staal F, Gallo RC (1985) HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 227:177–182

    Google Scholar 

  26. Snider WD, Simpson DM, Nielsen S, Gold JWM, Metroka CE, Posner JB (1983) Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neurol 14:403–418

    Google Scholar 

  27. Stoler MH, Eskin TA, Benn S, Angerer RC, Angerer LM (1986) Human T-cell lymphotropic virus type III infection of the central nervous system: a preliminary in situ analysis. J Am Med Assoc 256:2360–2364

    Google Scholar 

  28. Vazeux R, Brousse N, Jarry A, Henin 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

    Google Scholar 

  29. 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

    Google Scholar 

  30. Weiner LP, Herndon RM, Narayan O, Johnson RT, Shah K, Rubinstein LJ, Preziosi TJ, Conley FK (1972) Isolation of virus related to SV40 from patients with progressive multifocal leukoencephalopathy. N Engl J Med 286:385–390

    Google Scholar 

  31. Wiley CA, Nelson JA (1988) Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis. Am J Pathol (in press)

  32. Wiley CA, Schrier RA, 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

    Google Scholar 

  33. Wiley CA, Oldstone MBA, Nelson JA (1987) Pathogenesis of AIDS encephalitis. J Neuropathol Exp Neurol (Abstr) 46:348

    Google Scholar 

  34. Wright CM, Felber BK, Paskalis H, Pavlakis GN (1986) Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science 234:988–992

    Google Scholar 

  35. Zagury D, Bernard J, Leonard R, Cheynier R, Feldman M, Sarin PS, Gallo RC (1986) Long-term cultures of HTLV-III-infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science 231:850–853

    Google Scholar 

  36. ZuRhein GM, Chou SM (1965) Particles resembling papovavirus in human cerebral demyelinating disease. Science 148:1477–1479

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology M-012, University of California, San Diego, School of Medicine, 92 093, La Jolla, CA, USA

    C. A. Wiley & M. Grafe

  2. Department of Internal Medicine, University of California, San Diego, School of Medicine, 92 093, La Jolla, CA, USA

    C. Kennedy

  3. Scripps Clinic and Research Foundation, La Jolla, Calif., USA

    J. A. Nelson

Authors
  1. C. A. Wiley
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  2. M. Grafe
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  3. C. Kennedy
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  4. J. A. Nelson
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Additional information

Supported by grants from the University of California AIDS Task Force to CAW and JAN. CAW is the recipient of a University of California Academic Senate Award RK211-M and a Teacher Investigator Development Award from NIH NINCDS (NS-00 928). JAN is supported by American Cancer Society Junior Award JFRA-115. Also supported in part by U.S. Public Health Service Grant AG-04342

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Wiley, C.A., Grafe, M., Kennedy, C. et al. Human immunodeficiency virus (HIV) and JC virus in acquired immune deficiency syndrome (AIDS) patients with progressive multifocal leukoencephalopathy. Acta Neuropathol 76, 338–346 (1988). https://doi.org/10.1007/BF00686970

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  • DOI: https://doi.org/10.1007/BF00686970

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