Abstract
Human immunodeficiency virus (HIV) RNA and proteins were detected in the brains of several AIDS patients with subacute encephalitis, by in situ hybridization and immunohistology. The majority of infected cells were mononucleated and bore processes. Using single and double immunohistologic procedures, the authors identified these cells as macrophages. The majority of them had the phenotype of microglial cells (Leu-M3-, CD4-), others were labeled with markers of circulating macrophages (Leu-M3+, CD4+/-). The presence of HIV RNA and proteins in CD4- cells could be explained by depressed CD4 antigen expression, as a result of infection or macrophage tissue differentiation.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Biondi A., Rossing T. H., Bennett J., Todd R. F., 3rd Surface membrane heterogeneity among human mononuclear phagocytes. J Immunol. 1984 Mar;132(3):1237–1243. [PubMed] [Google Scholar]
- 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]
- Brahic M., Stowring L., Ventura P., Haase A. T. Gene expression in visna virus infection in sheep. Nature. 1981 Jul 16;292(5820):240–242. doi: 10.1038/292240a0. [DOI] [PubMed] [Google Scholar]
- Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
- Dimitriu-Bona A., Burmester G. R., Waters S. J., Winchester R. J. Human mononuclear phagocyte differentiation antigens. I. Patterns of antigenic expression on the surface of human monocytes and macrophages defined by monoclonal antibodies. J Immunol. 1983 Jan;130(1):145–152. [PubMed] [Google Scholar]
- 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]
- Franklin W. A., Mason D. Y., Pulford K., Falini B., Bliss E., Gatter K. C., Stein H., Clarke L. C., McGee J. O. Immunohistological analysis of human mononuclear phagocytes and dendritic cells by using monoclonal antibodies. Lab Invest. 1986 Mar;54(3):322–335. [PubMed] [Google Scholar]
- 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]
- Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
- Gendelman H. E., Narayan O., Molineaux S., Clements J. E., Ghotbi Z. Slow, persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7086–7090. doi: 10.1073/pnas.82.20.7086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haase A. T., Stowring L., Narayan P., Griffin D., Price D. Slow persistent infection caused by visna virus: role of host restriction. Science. 1977 Jan 14;195(4274):175–177. doi: 10.1126/science.188133. [DOI] [PubMed] [Google Scholar]
- Hancock W. W., Zola H., Atkins R. C. Antigenic heterogeneity of human mononuclear phagocytes: immunohistologic analysis using monoclonal antibodies. Blood. 1983 Dec;62(6):1271–1279. [PubMed] [Google Scholar]
- Ho D. D., Rota T. R., Schooley R. T., Kaplan J. C., Allan J. D., Groopman J. E., Resnick L., Felsenstein D., Andrews C. A., Hirsch M. S. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med. 1985 Dec 12;313(24):1493–1497. doi: 10.1056/NEJM198512123132401. [DOI] [PubMed] [Google Scholar]
- Hoxie J. A., Haggarty B. S., Rackowski J. L., Pillsbury N., Levy J. A. Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. Science. 1985 Sep 27;229(4720):1400–1402. doi: 10.1126/science.2994222. [DOI] [PubMed] [Google Scholar]
- Hume D. A., Perry V. H., Gordon S. Immunohistochemical localization of a macrophage-specific antigen in developing mouse retina: phagocytosis of dying neurons and differentiation of microglial cells to form a regular array in the plexiform layers. J Cell Biol. 1983 Jul;97(1):253–257. doi: 10.1083/jcb.97.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Ling E. A., Penney D., Leblond C. P. Use of carbon labeling to demonstrate the role of blood monocytes as precursors of the 'ameboid cells' present in the corpus callosum of postnatal rats. J Comp Neurol. 1980 Oct 1;193(3):631–657. doi: 10.1002/cne.901930304. [DOI] [PubMed] [Google Scholar]
- Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
- Michelson S., Tardy-Panit M., Bârzu O. Properties of a human cytomegalovirus-induced protein kinase. Virology. 1984 Apr 30;134(2):259–268. doi: 10.1016/0042-6822(84)90295-2. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Schelper R. L., Adrian E. K., Jr Monocytes become macrophages; they do not become microglia: a light and electron microscopic autoradiographic study using 125-iododeoxyuridine. J Neuropathol Exp Neurol. 1986 Jan;45(1):1–19. doi: 10.1097/00005072-198601000-00001. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Stein H., Gerdes J., Schwab U., Lemke H., Mason D. Y., Ziegler A., Schienle W., Diehl V. Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population. Int J Cancer. 1982 Oct 15;30(4):445–459. doi: 10.1002/ijc.2910300411. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Wood G. S., Turner R. R., Shiurba R. A., Eng L., Warnke R. A. Human dendritic cells and macrophages. In situ immunophenotypic definition of subsets that exhibit specific morphologic and microenvironmental characteristics. Am J Pathol. 1985 Apr;119(1):73–82. [PMC free article] [PubMed] [Google Scholar]
- Wood G. S., Warner N. L., Warnke R. A. Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol. 1983 Jul;131(1):212–216. [PubMed] [Google Scholar]