Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1989 May;52(5):583–590. doi: 10.1136/jnnp.52.5.583

Examination of brains of AIDS cases for human immunodeficiency virus and human cytomegalovirus nucleic acids.

D G Walker 1, S Itagaki 1, K Berry 1, P L McGeer 1
PMCID: PMC1032164  PMID: 2543795

Abstract

The role of direct virus infection as a determining factor in acquired immunodeficiency syndrome (AIDS) dementia was investigated using in situ hybridisation for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV). Four of the five AIDS dementia patients in this series demonstrated HIV infected cells distributed in widely different parts of the brain, but only one case showed HCMV infected cells. The greater abundance of HIV was in subcortical white matter in nodular areas consisting of monocyte/macrophage infiltrates. The cells were occasionally arranged as a multinucleated syncitium. In two cases, a few large cells with the appearance of neurons were positive for HIV hybridisation. By appropriate treatment with ribonuclease, it was shown that hybridisation was primarily to HIV RNA. HCMV infected cells were observed in small numbers in only one of the positive cases, suggesting that HCMV is not a determining factor in AIDS dementia. HCMV positive cells were located in the grey matter, with an appearance suggestive of neurons. Cells expressing the MHC-class II antigen HLA-DR, a marker of reactive microglia and macrophages, were observed to be extensive in affected brain sections in the one case examined. These cells were present in greater number than HIV infected cells. In this case, extensive numbers of HIV infected cells were noticed along the peripheral margin of the substantia innominata. This could indicate infection in this case of a critical brain region from the cerebrospinal fluid.

Full text

PDF
583

Images in this article

586Image
on p.586
587Image
on p.587
587Image
on p.587
587Image
on p.587
588Image
on p.588
589Image
on p.589

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anand R. Natural variants of human immunodeficiency virus from patients with neurological disorders do not kill T4+ cells. Ann Neurol. 1988;23 (Suppl):S66–S70. doi: 10.1002/ana.410230718. [DOI] [PubMed] [Google Scholar]
  2. Boyes B. E., Walker D. G., McGeer P. L. Separation of large DNA restriction fragments on a size-exclusion column by a nonideal mechanism. Anal Biochem. 1988 Apr;170(1):127–134. doi: 10.1016/0003-2697(88)90099-1. [DOI] [PubMed] [Google Scholar]
  3. Brigati D. J., Myerson D., Leary J. J., Spalholz B., Travis S. Z., Fong C. K., Hsiung G. D., Ward D. C. Detection of viral genomes in cultured cells and paraffin-embedded tissue sections using biotin-labeled hybridization probes. Virology. 1983 Apr 15;126(1):32–50. doi: 10.1016/0042-6822(83)90460-9. [DOI] [PubMed] [Google Scholar]
  4. Budka H., Costanzi G., Cristina S., Lechi A., Parravicini C., Trabattoni R., Vago L. Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases. Acta Neuropathol. 1987;75(2):185–198. doi: 10.1007/BF00687080. [DOI] [PubMed] [Google Scholar]
  5. Cheng-Mayer C., Levy J. A. Distinct biological and serological properties of human immunodeficiency viruses from the brain. Ann Neurol. 1988;23 (Suppl):S58–S61. doi: 10.1002/ana.410230716. [DOI] [PubMed] [Google Scholar]
  6. Elder G. A., Sever J. L. Neurologic disorders associated with AIDS retroviral infection. Rev Infect Dis. 1988 Mar-Apr;10(2):286–302. doi: 10.1093/clinids/10.2.286. [DOI] [PubMed] [Google Scholar]
  7. Faulstich M. E. Acquired immune deficiency syndrome: an overview of central nervous system complications and neuropsychological sequelae. Int J Neurosci. 1986 Nov;30(4):249–254. doi: 10.3109/00207458608985675. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  9. Funke I., Hahn A., Rieber E. P., 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. 1987 Apr 1;165(4):1230–1235. doi: 10.1084/jem.165.4.1230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gabuzda D. H., Ho D. D., de la Monte S. M., Hirsch M. S., Rota T. R., Sobel R. A. Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS. Ann Neurol. 1986 Sep;20(3):289–295. doi: 10.1002/ana.410200304. [DOI] [PubMed] [Google Scholar]
  11. Gartner S., Markovits P., Markovitz D. M., Betts R. F., Popovic M. Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. JAMA. 1986 Nov 7;256(17):2365–2371. [PubMed] [Google Scholar]
  12. Hill J. M., Farrar W. L., Pert C. B. Autoradiographic localization of T4 antigen, the HIV receptor, in human brain. Int J Neurosci. 1987 Feb;32(3-4):687–693. doi: 10.3109/00207458709043323. [DOI] [PubMed] [Google Scholar]
  13. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. doi: 10.1126/science.3016903. [DOI] [PubMed] [Google Scholar]
  14. Luciw P. A., Potter S. J., Steimer K., Dina D., Levy J. A. Molecular cloning of AIDS-associated retrovirus. Nature. 1984 Dec 20;312(5996):760–763. doi: 10.1038/312760a0. [DOI] [PubMed] [Google Scholar]
  15. McGeer P. L., Itagaki S., Tago H., McGeer E. G. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett. 1987 Aug 18;79(1-2):195–200. doi: 10.1016/0304-3940(87)90696-3. [DOI] [PubMed] [Google Scholar]
  16. McGeer P. L., McGeer E. G., Suzuki J., Dolman C. E., Nagai T. Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain. Neurology. 1984 Jun;34(6):741–745. doi: 10.1212/wnl.34.6.741. [DOI] [PubMed] [Google Scholar]
  17. Navia B. A., Cho E. S., Petito C. K., Price R. W. The AIDS dementia complex: II. Neuropathology. Ann Neurol. 1986 Jun;19(6):525–535. doi: 10.1002/ana.410190603. [DOI] [PubMed] [Google Scholar]
  18. Navia B. A., Jordan B. D., Price R. W. The AIDS dementia complex: I. Clinical features. Ann Neurol. 1986 Jun;19(6):517–524. doi: 10.1002/ana.410190602. [DOI] [PubMed] [Google Scholar]
  19. Navia B. A., Price R. W. The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection. Arch Neurol. 1987 Jan;44(1):65–69. doi: 10.1001/archneur.1987.00520130051017. [DOI] [PubMed] [Google Scholar]
  20. Nielsen S. L., Petito C. K., Urmacher C. D., Posner J. B. Subacute encephalitis in acquired immune deficiency syndrome: a postmortem study. Am J Clin Pathol. 1984 Dec;82(6):678–682. doi: 10.1093/ajcp/82.6.678. [DOI] [PubMed] [Google Scholar]
  21. Perry S., Marotta R. F. AIDS dementia: a review of the literature. Alzheimer Dis Assoc Disord. 1987;1(4):221–235. doi: 10.1097/00002093-198701040-00002. [DOI] [PubMed] [Google Scholar]
  22. Pert C. B., Smith C. C., Ruff M. R., Hill J. M. AIDS and its dementia as a neuropeptide disorder: role of VIP receptor blockade by human immunodeficiency virus envelope. Ann Neurol. 1988;23 (Suppl):S71–S73. doi: 10.1002/ana.410230719. [DOI] [PubMed] [Google Scholar]
  23. Petito C. K., Cho E. S., Lemann W., Navia B. A., Price R. W. Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review. J Neuropathol Exp Neurol. 1986 Nov;45(6):635–646. doi: 10.1097/00005072-198611000-00003. [DOI] [PubMed] [Google Scholar]
  24. Pumarola-Sune T., Navia B. A., Cordon-Cardo C., Cho E. S., Price R. W. HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol. 1987 May;21(5):490–496. doi: 10.1002/ana.410210513. [DOI] [PubMed] [Google Scholar]
  25. Rüger R., Bornkamm G. W., Fleckenstein B. Human cytomegalovirus DNA sequences with homologies to the cellular genome. J Gen Virol. 1984 Aug;65(Pt 8):1351–1364. doi: 10.1099/0022-1317-65-8-1351. [DOI] [PubMed] [Google Scholar]
  26. Schrier R. D., Rice G. P., Oldstone M. B. Suppression of natural killer cell activity and T cell proliferation by fresh isolates of human cytomegalovirus. J Infect Dis. 1986 Jun;153(6):1084–1091. doi: 10.1093/infdis/153.6.1084. [DOI] [PubMed] [Google Scholar]
  27. Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
  28. Stoler M. H., Eskin T. A., Benn S., Angerer R. C., Angerer L. M. Human T-cell lymphotropic virus type III infection of the central nervous system. A preliminary in situ analysis. JAMA. 1986 Nov 7;256(17):2360–2364. [PubMed] [Google Scholar]
  29. Vazeux R., Brousse N., Jarry A., Henin D., Marche C., Vedrenne C., Mikol J., Wolff M., Michon C., Rozenbaum W. AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol. 1987 Mar;126(3):403–410. [PMC free article] [PubMed] [Google Scholar]
  30. Wiley C. A. Implications of the neuropathology of HIV encephalitis for the pathogenesis of Alzheimer disease. Alzheimer Dis Assoc Disord. 1987;1(4):236–250. doi: 10.1097/00002093-198701040-00003. [DOI] [PubMed] [Google Scholar]
  31. Wiley C. A., Schrier R. D., Nelson J. A., Lampert P. W., Oldstone M. B. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089–7093. doi: 10.1073/pnas.83.18.7089. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES