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. 1992 Jan;140(1):137–144.

Low levels of human immunodeficiency virus replication in the brain tissue of children with severe acquired immunodeficiency syndrome encephalopathy.

R Vazeux 1, C Lacroix-Ciaudo 1, S Blanche 1, M C Cumont 1, D Henin 1, F Gray 1, L Boccon-Gibod 1, M Tardieu 1
PMCID: PMC1886254  PMID: 1731520

Abstract

The authors examined the autopsy brain samples of nine children infected with human immunodeficiency virus (HIV) at birth by histology, immunologic staining, and in situ hybridization. Surprisingly, although seven of these children presented with typical AIDS encephalopathy, the authors could detect a multifocal HIV infection in the brains of only three of these patients. The authors could not detect any significant HIV replication in the brain of four other children despite severe neurologic disease. However, HIV DNA was detected by polymerase chain reaction (PCR) in the central nervous system (CNS) of all patients. In addition, the authors found associated lesions in the brains of three of these four patients. This study shows that severe AIDS encephalopathy exists in children and therefore might exist in adults with few signs or without any signs of HIV replication or inflammation in the CNS. Understanding the pathogenesis of this neurologic disease and the kinetics of HIV replication in brain tissue of children with AIDS encephalopathy is essential to determine the best therapeutic strategy.

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Selected References

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

  1. Belman A. L., Diamond G., Dickson D., Horoupian D., Llena J., Lantos G., Rubinstein A. Pediatric acquired immunodeficiency syndrome. Neurologic syndromes. Am J Dis Child. 1988 Jan;142(1):29–35. doi: 10.1001/archpedi.1988.02150010039017. [DOI] [PubMed] [Google Scholar]
  2. Belman A. L., Lantos G., Horoupian D., Novick B. E., Ultmann M. H., Dickson D. W., Rubinstein A. AIDS: calcification of the basal ganglia in infants and children. Neurology. 1986 Sep;36(9):1192–1199. doi: 10.1212/wnl.36.9.1192. [DOI] [PubMed] [Google Scholar]
  3. Belman A. L., Ultmann M. H., Horoupian D., Novick B., Spiro A. J., Rubinstein A., Kurtzberg D., Cone-Wesson B. Neurological complications in infants and children with acquired immune deficiency syndrome. Ann Neurol. 1985 Nov;18(5):560–566. doi: 10.1002/ana.410180509. [DOI] [PubMed] [Google Scholar]
  4. Blanche S., Rouzioux C., Moscato M. L., Veber F., Mayaux M. J., Jacomet C., Tricoire J., Deville A., Vial M., Firtion G. A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. HIV Infection in Newborns French Collaborative Study Group. N Engl J Med. 1989 Jun 22;320(25):1643–1648. doi: 10.1056/NEJM198906223202502. [DOI] [PubMed] [Google Scholar]
  5. Blanche S., Tardieu M., Duliege A., Rouzioux C., Le Deist F., Fukunaga K., Caniglia M., Jacomet C., Messiah A., Griscelli C. Longitudinal study of 94 symptomatic infants with perinatally acquired human immunodeficiency virus infection. Evidence for a bimodal expression of clinical and biological symptoms. Am J Dis Child. 1990 Nov;144(11):1210–1215. doi: 10.1001/archpedi.1990.02150350042021. [DOI] [PubMed] [Google Scholar]
  6. Dreyer E. B., Kaiser P. K., Offermann J. T., Lipton S. A. HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science. 1990 Apr 20;248(4953):364–367. doi: 10.1126/science.2326646. [DOI] [PubMed] [Google Scholar]
  7. Epstein L. G., Sharer L. R., Goudsmit J. Neurological and neuropathological features of human immunodeficiency virus infection in children. Ann Neurol. 1988;23 (Suppl):S19–S23. doi: 10.1002/ana.410230709. [DOI] [PubMed] [Google Scholar]
  8. Epstein L. G., Sharer L. R., Joshi V. V., Fojas M. M., Koenigsberger M. R., Oleske J. M. Progressive encephalopathy in children with acquired immune deficiency syndrome. Ann Neurol. 1985 May;17(5):488–496. doi: 10.1002/ana.410170512. [DOI] [PubMed] [Google Scholar]
  9. Epstein L. G., Sharer L. R., Oleske J. M., Connor E. M., Goudsmit J., Bagdon L., Robert-Guroff M., Koenigsberger M. R. Neurologic manifestations of human immunodeficiency virus infection in children. Pediatrics. 1986 Oct;78(4):678–687. [PubMed] [Google Scholar]
  10. Haase A. T. Pathogenesis of lentivirus infections. Nature. 1986 Jul 10;322(6075):130–136. doi: 10.1038/322130a0. [DOI] [PubMed] [Google Scholar]
  11. Lee M. R., Ho D. D., Gurney M. E. Functional interaction and partial homology between human immunodeficiency virus and neuroleukin. Science. 1987 Aug 28;237(4818):1047–1051. doi: 10.1126/science.3039662. [DOI] [PubMed] [Google Scholar]
  12. Levy R. M., Bredesen D. E., Rosenblum M. L. Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg. 1985 Apr;62(4):475–495. doi: 10.3171/jns.1985.62.4.0475. [DOI] [PubMed] [Google Scholar]
  13. McArthur J. C., Becker P. S., Parisi J. E., Trapp B., Selnes O. A., Cornblath D. R., Balakrishnan J., Griffin J. W., Price D. Neuropathological changes in early HIV-1 dementia. Ann Neurol. 1989 Nov;26(5):681–684. doi: 10.1002/ana.410260516. [DOI] [PubMed] [Google Scholar]
  14. Merrill J. E., Koyanagi Y., Chen I. S. Interleukin-1 and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. J Virol. 1989 Oct;63(10):4404–4408. doi: 10.1128/jvi.63.10.4404-4408.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Meyenhofer M. F., Epstein L. G., Cho E. S., Sharer L. R. Ultrastructural morphology and intracellular production of human immunodeficiency virus (HIV) in brain. J Neuropathol Exp Neurol. 1987 Jul;46(4):474–484. doi: 10.1097/00005072-198707000-00006. [DOI] [PubMed] [Google Scholar]
  16. Mok J. Q., Giaquinto C., De Rossi A., Grosch-Wörner I., Ades A. E., Peckham C. S. Infants born to mothers seropositive for human immunodeficiency virus. Preliminary findings from a multicentre European study. Lancet. 1987 May 23;1(8543):1164–1168. doi: 10.1016/s0140-6736(87)92142-8. [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. Ou C. Y., Kwok S., Mitchell S. W., Mack D. H., Sninsky J. J., Krebs J. W., Feorino P., Warfield D., Schochetman G. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988 Jan 15;239(4837):295–297. doi: 10.1126/science.3336784. [DOI] [PubMed] [Google Scholar]
  19. Pang S., Koyanagi Y., Miles S., Wiley C., Vinters H. V., Chen I. S. High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature. 1990 Jan 4;343(6253):85–89. doi: 10.1038/343085a0. [DOI] [PubMed] [Google Scholar]
  20. Perry V. H., Hume D. A., Gordon S. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience. 1985 Jun;15(2):313–326. doi: 10.1016/0306-4522(85)90215-5. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Pizzo P. A., Eddy J., Falloon J., Balis F. M., Murphy R. F., Moss H., Wolters P., Brouwers P., Jarosinski P., Rubin M. Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. N Engl J Med. 1988 Oct 6;319(14):889–896. doi: 10.1056/NEJM198810063191401. [DOI] [PubMed] [Google Scholar]
  23. Price R. W., Brew B., Sidtis J., Rosenblum M., Scheck A. C., Cleary P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science. 1988 Feb 5;239(4840):586–592. doi: 10.1126/science.3277272. [DOI] [PubMed] [Google Scholar]
  24. Ryder R. W., Nsa W., Hassig S. E., Behets F., Rayfield M., Ekungola B., Nelson A. M., Mulenda U., Francis H., Mwandagalirwa K. Perinatal transmission of the human immunodeficiency virus type 1 to infants of seropositive women in Zaire. N Engl J Med. 1989 Jun 22;320(25):1637–1642. doi: 10.1056/NEJM198906223202501. [DOI] [PubMed] [Google Scholar]
  25. Scott G. B., Hutto C., Makuch R. W., Mastrucci M. T., O'Connor T., Mitchell C. D., Trapido E. J., Parks W. P. Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. N Engl J Med. 1989 Dec 28;321(26):1791–1796. doi: 10.1056/NEJM198912283212604. [DOI] [PubMed] [Google Scholar]
  26. Selmaj K. W., Raine C. S. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988 Apr;23(4):339–346. doi: 10.1002/ana.410230405. [DOI] [PubMed] [Google Scholar]
  27. Sharer L. R., Epstein L. G., Cho E. S., Joshi V. V., Meyenhofer M. F., Rankin L. F., Petito C. K. Pathologic features of AIDS encephalopathy in children: evidence for LAV/HTLV-III infection of brain. Hum Pathol. 1986 Mar;17(3):271–284. doi: 10.1016/s0046-8177(83)80220-2. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Snider W. D., Simpson D. M., Nielsen S., Gold J. W., Metroka C. E., Posner J. B. Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neurol. 1983 Oct;14(4):403–418. doi: 10.1002/ana.410140404. [DOI] [PubMed] [Google Scholar]
  30. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Vazeux R., Cumont M., Girard P. M., Nassif X., Trotot P., Marche C., Matthiessen L., Vedrenne C., Mikol J., Henin D. Severe encephalitis resulting from coinfections with HIV and JC virus. Neurology. 1990 Jun;40(6):944–948. doi: 10.1212/wnl.40.6.944. [DOI] [PubMed] [Google Scholar]
  33. Watkins B. A., Dorn H. H., Kelly W. B., Armstrong R. C., Potts B. J., Michaels F., Kufta C. V., Dubois-Dalcq M. Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science. 1990 Aug 3;249(4968):549–553. doi: 10.1126/science.2200125. [DOI] [PubMed] [Google Scholar]
  34. Wiley C. A., Belman A. L., Dickson D. W., Rubinstein A., Nelson J. A. Human immunodeficiency virus within the brains of children with AIDS. Clin Neuropathol. 1990 Jan-Feb;9(1):1–6. [PubMed] [Google Scholar]

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