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. 1991 Dec;139(6):1273–1280.

Early viral replication in the brain of SIV-infected rhesus monkeys.

L Chakrabarti 1, M Hurtrel 1, M A Maire 1, R Vazeux 1, D Dormont 1, L Montagnier 1, B Hurtrel 1
PMCID: PMC1886455  PMID: 1750503

Abstract

To investigate the mechanism of simian immunodeficiency virus (SIV) entry into the central nervous system (CNS) and the initial events leading to neuropathogenesis, SIV replication was studied by in situ hybridization in the CNS of 5 Rhesus macaques at 7 days, 1, 2, and 3 months after SIV intravenous inoculation. CNS infection was found to be a frequent and early event, as SIV was detected in the CNS of all the animals studied and as early as 7 days postinoculation. At the earliest stage, the infection localized mainly to perivascular cells. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express the CD68 marker, suggesting that infected mononuclear phagocytes crossing the blood-brain barrier represent the main source of virus in the CNS. Early viral replication coincided with neuropathologic changes, consisting in gliosis, perivascular infiltrates and rare glial nodules. Immunophenotyping of brain tissue showed that increased macrophage infiltration, microglial reactivity and MHC class II induction occurred within the first week of infection, indicating a possible immunopathologic mechanism in early CNS pathogenesis.

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Selected References

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

  1. Artigas J., Niedobitek F., Grosse G., Heise W., Gosztonyi G. Spongiform encephalopathy in AIDS dementia complex: report of five cases. J Acquir Immune Defic Syndr. 1989;2(4):374–381. [PubMed] [Google Scholar]
  2. Brahic M., Haase A. T., Cash E. Simultaneous in situ detection of viral RNA and antigens. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5445–5448. doi: 10.1073/pnas.81.17.5445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carne C. A., Tedder R. S., Smith A., Sutherland S., Elkington S. G., Daly H. M., Preston F. E., Craske J. Acute encephalopathy coincident with seroconversion for anti-HTLV-III. Lancet. 1985 Nov 30;2(8466):1206–1208. doi: 10.1016/s0140-6736(85)90740-8. [DOI] [PubMed] [Google Scholar]
  4. Daniel M. D., Letvin N. L., King N. W., Kannagi M., Sehgal P. K., Hunt R. D., Kanki P. J., Essex M., Desrosiers R. C. Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Science. 1985 Jun 7;228(4704):1201–1204. doi: 10.1126/science.3159089. [DOI] [PubMed] [Google Scholar]
  5. Elder G. A., Sever J. L. AIDS and neurological disorders: an overview. Ann Neurol. 1988;23 (Suppl):S4–S6. doi: 10.1002/ana.410230705. [DOI] [PubMed] [Google Scholar]
  6. Epstein L. G. Lentiviral encephalitides in the immature host: a comparison of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) brain infection. Brain Dev. 1989;11(6):353–359. doi: 10.1016/s0387-7604(89)80016-6. [DOI] [PubMed] [Google Scholar]
  7. Esiri M. M., McGee J. O. Monoclonal antibody to macrophages (EMB/11) labels macrophages and microglial cells in human brain. J Clin Pathol. 1986 Jun;39(6):615–621. doi: 10.1136/jcp.39.6.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Franchini G., Gurgo C., Guo H. G., Gallo R. C., Collalti E., Fargnoli K. A., Hall L. F., Wong-Staal F., Reitz M. S., Jr Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses. Nature. 1987 Aug 6;328(6130):539–543. doi: 10.1038/328539a0. [DOI] [PubMed] [Google Scholar]
  9. Goudsmit J., Wolters E. C., Bakker M., Smit L., Van der Noordaa J., Hische E. A., Tutuarima J. A., Van der Helm H. J. Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex. Br Med J (Clin Res Ed) 1986 May 10;292(6530):1231–1234. doi: 10.1136/bmj.292.6530.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harouse J. M., Wroblewska Z., Laughlin M. A., Hickey W. F., Schonwetter B. S., Gonzalez-Scarano F. Human choroid plexus cells can be latently infected with human immunodeficiency virus. Ann Neurol. 1989 Apr;25(4):406–411. doi: 10.1002/ana.410250414. [DOI] [PubMed] [Google Scholar]
  11. Hertz L., McFarlin D. E., Waksman B. H. Astrocytes: auxiliary cells for immune responses in the central nervous system? Immunol Today. 1990 Aug;11(8):265–268. doi: 10.1016/0167-5699(90)90106-j. [DOI] [PubMed] [Google Scholar]
  12. Hickey W. F., Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988 Jan 15;239(4837):290–292. doi: 10.1126/science.3276004. [DOI] [PubMed] [Google Scholar]
  13. Hirsch V., Riedel N., Mullins J. I. The genome organization of STLV-3 is similar to that of the AIDS virus except for a truncated transmembrane protein. Cell. 1987 May 8;49(3):307–319. doi: 10.1016/0092-8674(87)90283-2. [DOI] [PubMed] [Google Scholar]
  14. Ho D. D., Sarngadharan M. G., Resnick L., Dimarzoveronese F., Rota T. R., Hirsch M. S. Primary human T-lymphotropic virus type III infection. Ann Intern Med. 1985 Dec;103(6 ):880–883. doi: 10.7326/0003-4819-103-6-880. [DOI] [PubMed] [Google Scholar]
  15. Hollander H., Levy J. A. Neurologic abnormalities and recovery of human immunodeficiency virus from cerebrospinal fluid. Ann Intern Med. 1987 May;106(5):692–695. doi: 10.7326/0003-4819-106-5-692. [DOI] [PubMed] [Google Scholar]
  16. Hollander H., Stringari S. Human immunodeficiency virus-associated meningitis. Clinical course and correlations. Am J Med. 1987 Nov;83(5):813–816. doi: 10.1016/0002-9343(87)90635-8. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Koralnik I. J., Beaumanoir A., Häusler R., Kohler A., Safran A. B., Delacoux R., Vibert D., Mayer E., Burkhard P., Nahory A. A controlled study of early neurologic abnormalities in men with asymptomatic human immunodeficiency virus infection. N Engl J Med. 1990 Sep 27;323(13):864–870. doi: 10.1056/NEJM199009273231303. [DOI] [PubMed] [Google Scholar]
  19. Michaels J., Sharer L. R., Epstein L. G. Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review. Immunodefic Rev. 1988;1(1):71–104. [PubMed] [Google Scholar]
  20. Narayan O., Clements J. E. Biology and pathogenesis of lentiviruses. J Gen Virol. 1989 Jul;70(Pt 7):1617–1639. doi: 10.1099/0022-1317-70-7-1617. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Peluso R., Haase A., Stowring L., Edwards M., Ventura P. A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology. 1985 Nov;147(1):231–236. doi: 10.1016/0042-6822(85)90246-6. [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. Resnick L., diMarzo-Veronese F., Schüpbach J., Tourtellotte W. W., Ho D. D., Müller F., Shapshak P., Vogt M., Groopman J. E., Markham P. D. Intra-blood-brain-barrier synthesis of HTLV-III-specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex. N Engl J Med. 1985 Dec 12;313(24):1498–1504. doi: 10.1056/NEJM198512123132402. [DOI] [PubMed] [Google Scholar]
  25. Risau W., Wolburg H. Development of the blood-brain barrier. Trends Neurosci. 1990 May;13(5):174–178. doi: 10.1016/0166-2236(90)90043-a. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Tindall B., Cooper D. A. Primary HIV infection: host responses and intervention strategies. AIDS. 1991 Jan;5(1):1–14. [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Weiser B., Peress N., La Neve D., Eilbott D. J., Seidman R., Burger H. Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. Proc Natl Acad Sci U S A. 1990 May;87(10):3997–4001. doi: 10.1073/pnas.87.10.3997. [DOI] [PMC free article] [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]

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