Abstract
The importance of macrophage infection for the development of acquired immune deficiency syndrome (AIDS) was investigated. Molecularly cloned simian immunodeficiency virus (SIV)mac239 replicates very poorly in cultured macrophages yet it causes AIDS in rhesus monkeys. Three of five rhesus monkeys that died with AIDS following SIVmac239 infection showed no disease manifestations directly associated with macrophage infection, such as encephalitis and granulomatous interstitial pneumonia. Simian immunodeficiency virus recovered from the peripheral blood of these three animals at or near the time of death replicated very poorly if at all in cultured macrophages, and tissues taken at autopsy showed little or no infection of macrophages by immunohistochemical staining. However two of the five rhesus monkeys that died with AIDS following SIVmac239 infection displayed a characteristic SIV-related meningoencephalitis and/or granulomatous pneumonia, lesions associated with macrophage infection. Simian immunodeficiency virus recovered from the peripheral blood of these two animals near the time of death replicated extremely well in cultured macrophages, indicating the emergency of macrophage-tropic variants in vivo. Furthermore tissues taken at autopsy from these two showed many infected macrophages by immunohistochemical staining. These results indicate that AIDS and death can occur without obvious involvement of macrophage infection. However the presence of macrophage-tropic viral strains appears to influence the disease course and disease manifestations.
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.
- Armstrong J. A., Horne R. Follicular dendritic cells and virus-like particles in AIDS-related lymphadenopathy. Lancet. 1984 Aug 18;2(8399):370–372. doi: 10.1016/s0140-6736(84)90540-3. [DOI] [PubMed] [Google Scholar]
- Autran B., Mayaud C. M., Raphael M., Plata F., Denis M., Bourguin A., Guillon J. M., Debre P., Akoun G. Evidence for a cytotoxic T-lymphocyte alveolitis in human immunodeficiency virus-infected patients. AIDS. 1988 Jun;2(3):179–183. [PubMed] [Google Scholar]
- Baskin G. B. Disseminated cytomegalovirus infection in immunodeficient rhesus monkeys. Am J Pathol. 1987 Nov;129(2):345–352. [PMC free article] [PubMed] [Google Scholar]
- Baskin G. B., Murphey-Corb M., Watson E. A., Martin L. N. Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/delta. Vet Pathol. 1988 Nov;25(6):456–467. doi: 10.1177/030098588802500609. [DOI] [PubMed] [Google Scholar]
- Cheng-Mayer C., Seto D., Tateno M., Levy J. A. Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988 Apr 1;240(4848):80–82. doi: 10.1126/science.2832945. [DOI] [PubMed] [Google Scholar]
- Collman R., Hassan N. F., Walker R., Godfrey B., Cutilli J., Hastings J. C., Friedman H., Douglas S. D., Nathanson N. Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types. J Exp Med. 1989 Oct 1;170(4):1149–1163. doi: 10.1084/jem.170.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Daniel M. D., Li Y., Naidu Y. M., Durda P. J., Schmidt D. K., Troup C. D., Silva D. P., MacKey J. J., Kestler H. W., 3rd, Sehgal P. K. Simian immunodeficiency virus from African green monkeys. J Virol. 1988 Nov;62(11):4123–4128. doi: 10.1128/jvi.62.11.4123-4128.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Desrosiers R. C., Ringler D. J. Use of simian immunodeficiency viruses for AIDS research. Intervirology. 1989;30(6):301–312. doi: 10.1159/000150108. [DOI] [PubMed] [Google Scholar]
- Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353–6357. doi: 10.1073/pnas.86.16.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duh E. J., Maury W. J., Folks T. M., Fauci A. S., Rabson A. B. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974–5978. doi: 10.1073/pnas.86.15.5974. [DOI] [PMC free article] [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]
- Kannagi M., Yetz J. M., Letvin N. L. In vitro growth characteristics of simian T-lymphotropic virus type III. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7053–7057. doi: 10.1073/pnas.82.20.7053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kestler H., Kodama T., Ringler D., Marthas M., Pedersen N., Lackner A., Regier D., Sehgal P., Daniel M., King N. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990 Jun 1;248(4959):1109–1112. doi: 10.1126/science.2160735. [DOI] [PubMed] [Google Scholar]
- King N. W., Chalifoux L. V., Ringler D. J., Wyand M. S., Sehgal P. K., Daniel M. D., Letvin N. L., Desrosiers R. C., Blake B. J., Hunt R. D. Comparative biology of natural and experimental SIVmac infection in macaque monkeys: a review. J Med Primatol. 1990;19(2):109–118. [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]
- Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
- Lairmore M. D., Akita G. Y., Russell H. I., DeMartini J. C. Replication and cytopathic effects of ovine lentivirus strains in alveolar macrophages correlate with in vivo pathogenicity. J Virol. 1987 Dec;61(12):4038–4042. doi: 10.1128/jvi.61.12.4038-4042.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Letvin N. L., Daniel M. D., Sehgal P. K., Desrosiers R. C., Hunt R. D., Waldron L. M., MacKey J. J., Schmidt D. K., Chalifoux L. V., King N. W. Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science. 1985 Oct 4;230(4721):71–73. doi: 10.1126/science.2412295. [DOI] [PubMed] [Google Scholar]
- Malim M. H., Böhnlein S., Fenrick R., Le S. Y., Maizel J. V., Cullen B. R. Functional comparison of the Rev trans-activators encoded by different primate immunodeficiency virus species. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8222–8226. doi: 10.1073/pnas.86.21.8222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Massari F. E., Poli G., Schnittman S. M., Psallidopoulos M. C., Davey V., Fauci A. S. In vivo T lymphocyte origin of macrophage-tropic strains of HIV. Role of monocytes during in vitro isolation and in vivo infection. J Immunol. 1990 Jun 15;144(12):4628–4632. [PubMed] [Google Scholar]
- 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]
- Minassian A. A., Kalyanaraman V. S., Gallo R. C., Popovic M. Monoclonal antibodies against human immunodeficiency virus (HIV) type 2 core proteins: cross-reactivity with HIV type 1 and simian immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6939–6943. doi: 10.1073/pnas.85.18.6939. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Naidu Y. M., Kestler H. W., 3rd, Li Y., Butler C. V., Silva D. P., Schmidt D. K., Troup C. D., Sehgal P. K., Sonigo P., Daniel M. D. Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac. J Virol. 1988 Dec;62(12):4691–4696. doi: 10.1128/jvi.62.12.4691-4696.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patterson S., Knight S. C. Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J Gen Virol. 1987 Apr;68(Pt 4):1177–1181. doi: 10.1099/0022-1317-68-4-1177. [DOI] [PubMed] [Google Scholar]
- Plata F., Autran B., Martins L. P., Wain-Hobson S., Raphaël M., Mayaud C., Denis M., Guillon J. M., Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
- Rappersberger K., Gartner S., Schenk P., Stingl G., Groh V., Tschachler E., Mann D. L., Wolff K., Konrad K., Popovic M. Langerhans' cells are an actual site of HIV-1 replication. Intervirology. 1988;29(4):185–194. doi: 10.1159/000150045. [DOI] [PubMed] [Google Scholar]
- Regier D. A., Desrosiers R. C. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221–1231. doi: 10.1089/aid.1990.6.1221. [DOI] [PubMed] [Google Scholar]
- Ringler D. J., Hunt R. D., Desrosiers R. C., Daniel M. D., Chalifoux L. V., King N. W. Simian immunodeficiency virus-induced meningoencephalitis: natural history and retrospective study. Ann Neurol. 1988;23 (Suppl):S101–S107. doi: 10.1002/ana.410230726. [DOI] [PubMed] [Google Scholar]
- Ringler D. J., Walsh D. G., Chalifoux L. V., MacKey J. J., Daniel M. D., Desrosiers R. C., King N. W., Hancock W. W. Soluble and membrane-associated interleukin 2 receptor-alpha expression in rhesus monkeys infected with simian immunodeficiency virus. Lab Invest. 1990 Apr;62(4):435–443. [PubMed] [Google Scholar]
- Ringler D. J., Walsh D. G., MacKey J. J., Hunt R. D., King N. W. Immunophenotypic characterization of mononuclear phagocytes and dendritic cells in lymphoid organs of the rhesus monkey. Clin Immunol Immunopathol. 1988 Dec;49(3):349–364. doi: 10.1016/0090-1229(88)90125-0. [DOI] [PubMed] [Google Scholar]
- Ringler D. J., Wyand M. S., Walsh D. G., MacKey J. J., Chalifoux L. V., Popovic M., Minassian A. A., Sehgal P. K., Daniel M. D., Desrosiers R. C. Cellular localization of simian immunodeficiency virus in lymphoid tissues. I. Immunohistochemistry and electron microscopy. Am J Pathol. 1989 Feb;134(2):373–383. [PMC free article] [PubMed] [Google Scholar]
- Ringler D. J., Wyand M. S., Walsh D. G., MacKey J. J., Sehgal P. K., Daniel M. D., Desrosiers R. C., King N. W. The productive infection of alveolar macrophages by simian immunodeficiency virus. J Med Primatol. 1989;18(3-4):217–226. [PubMed] [Google Scholar]
- Sakai H., Shibata R., Miura T., Hayami M., Ogawa K., Kiyomasu T., Ishimoto A., Adachi A. Complementation of the rev gene mutation among human and simian lentiviruses. J Virol. 1990 May;64(5):2202–2207. doi: 10.1128/jvi.64.5.2202-2207.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tenner-Rácz K., Rácz P., Dietrich M., Kern P. Altered follicular dendritic cells and virus-like particles in AIDS and AIDS-related lymphadenopathy. Lancet. 1985 Jan 12;1(8420):105–106. doi: 10.1016/s0140-6736(85)91994-4. [DOI] [PubMed] [Google Scholar]
- Viglianti G. A., Sharma P. L., Mullins J. I. Simian immunodeficiency virus displays complex patterns of RNA splicing. J Virol. 1990 Sep;64(9):4207–4216. doi: 10.1128/jvi.64.9.4207-4216.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wyand M. S., Ringler D. J., Naidu Y. M., Mattmuller M., Chalifoux L. V., Sehgal P. K., Daniel M. D., Desrosiers R. C., King N. W. Cellular localization of simian immunodeficiency virus in lymphoid tissues. II. In situ hybridization. Am J Pathol. 1989 Feb;134(2):385–393. [PMC free article] [PubMed] [Google Scholar]

