Abstract
The pathogenesis of hematopoietic abnormalities associated with infection of susceptible hosts with either simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) is not fully understood. To determine if bone marrow cells are infected with SIV and if the pattern of viral infection is correlated with the severity of disease and abnormalities in hematopoiesis, 23 SIV-infected rhesus monkeys were examined by immunohistochemistry and in situ hybridization. By immunohistochemistry, only four monkeys were positive for SIV core protein p27, while in situ hybridization revealed viral RNA in the bone marrow of 15 monkeys. Simian immunodeficiency virus RNA was consistently expressed in the bone marrow from monkeys with severe lymphoid depletion (11 of 11), but less so in monkeys with follicular hyperplasia (0 of 2) or mild lymphoid depletion (4 of 10). In animals with mild lymphoid depletion, bone marrow cells infected with SIV were mainly mononuclear cells that appeared to be of myelomonocytic lineage. In contrast, monkeys with severe lymphoid depletion had SIV RNA localized to larger mononuclear cells with abundant cytoplasm often located in small lucent areas of the stroma. These SIV RNA-positive mononuclear cells were positive for the macrophage determinant CD68 as demonstrated by immunohistochemistry. Furthermore the stage of simian acquired immune deficiency syndrome, as indicated by lymphoid morphology, and SIV localization in the bone marrow were correlated with the incidence of anemia, bone marrow hyperplasia, and abnormal distribution of macrophages in the bone marrow. These results indicate that, in common with other animal lentiviral infections, the macrophage is a major target of SIV infections in the bone marrow.
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.
- Abraham N. G., Bucher D., Niranjan U., Brown A. C., Lutton J. D., Distenfeld A., Ahmed T., Levere R. D. Microenvironmental toxicity of azidothymidine: partial sparing with hemin. Blood. 1989 Jul;74(1):139–144. [PubMed] [Google Scholar]
- Baba T. W., Humphries E. H. Selective integration of avian leukosis virus in different hematopoietic tissues. Virology. 1986 Dec;155(2):557–566. doi: 10.1016/0042-6822(86)90216-3. [DOI] [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]
- Benveniste R. E., Morton W. R., Clark E. A., Tsai C. C., Ochs H. D., Ward J. M., Kuller L., Knott W. B., Hill R. W., Gale M. J. Inoculation of baboons and macaques with simian immunodeficiency virus/Mne, a primate lentivirus closely related to human immunodeficiency virus type 2. J Virol. 1988 Jun;62(6):2091–2101. doi: 10.1128/jvi.62.6.2091-2101.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berman E., Duigou-Osterndorf R., Krown S. E., Fanucchi M. P., Chou J., Hirsch M. S., Clarkson B. D., Chou T. C. Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells. Blood. 1989 Sep;74(4):1281–1286. [PubMed] [Google Scholar]
- Biberfeld P., Porwit-Ksiazek A., Böttiger B., Morfeldt-Månsson L., Biberfeld G. Immunohistopathology of lymph nodes in HTLV-III infected homosexuals with persistent adenopathy or AIDS. Cancer Res. 1985 Sep;45(9 Suppl):4665s–4670s. [PubMed] [Google Scholar]
- Castella A., Croxson T. S., Mildvan D., Witt D. H., Zalusky R. The bone marrow in AIDS. A histologic, hematologic, and microbiologic study. Am J Clin Pathol. 1985 Oct;84(4):425–432. doi: 10.1093/ajcp/84.4.425. [DOI] [PubMed] [Google Scholar]
- Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
- Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
- Chalifoux L. V., Ringler D. J., King N. W., Sehgal P. K., Desrosiers R. C., Daniel M. D., Letvin N. L. Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV). Am J Pathol. 1987 Jul;128(1):104–110. [PMC free article] [PubMed] [Google Scholar]
- Dainiak N., Worthington M., Riordan M. A., Kreczko S., Goldman L. 3'-Azido-3'-deoxythymidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells. Br J Haematol. 1988 Jul;69(3):299–304. doi: 10.1111/j.1365-2141.1988.tb02366.x. [DOI] [PubMed] [Google Scholar]
- Daniel M. D., Letvin N. L., Sehgal P. K., Hunsmann G., Schmidt D. K., King N. W., Desrosiers R. C. Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus. J Gen Virol. 1987 Dec;68(Pt 12):3183–3189. doi: 10.1099/0022-1317-68-12-3183. [DOI] [PubMed] [Google Scholar]
- Davis B. R., Brightman B. K., Chandy K. G., Fan H. Characterization of a preleukemic state induced by Moloney murine leukemia virus: evidence for two infection events during leukemogenesis. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4875–4879. doi: 10.1073/pnas.84.14.4875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delacrétaz F., Perey L., Schmidt P. M., Chave J. P., Costa J. Histopathology of bone marrow in human immunodeficiency virus infection. Virchows Arch A Pathol Anat Histopathol. 1987;411(6):543–551. doi: 10.1007/BF00713285. [DOI] [PubMed] [Google Scholar]
- Diebold J., Marche C., Audouin J., Aubert J. P., Le Tourneau A., Bouton C., Reynes M., Wizniak J., Capron F., Tricottet V. Lymph node modification in patients with the acquired immunodeficiency syndrome (AIDS) or with AIDS related complex (ARC). A histological, immuno-histopathological and ultrastructural study of 45 cases. Pathol Res Pract. 1985 Dec;180(6):590–611. doi: 10.1016/S0344-0338(85)80037-6. [DOI] [PubMed] [Google Scholar]
- Donahue R. E., Johnson M. M., Zon L. I., Clark S. C., Groopman J. E. Suppression of in vitro haematopoiesis following human immunodeficiency virus infection. Nature. 1987 Mar 12;326(6109):200–203. doi: 10.1038/326200a0. [DOI] [PubMed] [Google Scholar]
- Folks T. M., Kessler S. W., Orenstein J. M., Justement J. S., Jaffe E. S., Fauci A. S. Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow. Science. 1988 Nov 11;242(4880):919–922. doi: 10.1126/science.2460922. [DOI] [PubMed] [Google Scholar]
- 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]
- Gardner M. B., Luciw P. A. Simian immunodeficiency viruses and their relationship to the human immunodeficiency viruses. AIDS. 1988;2 (Suppl 1):S3–10. doi: 10.1097/00002030-198800001-00002. [DOI] [PubMed] [Google Scholar]
- Gardner M. B., Luciw P., Lerche N., Marx P. Nonhuman primate retrovirus isolates and AIDS. Adv Vet Sci Comp Med. 1988;32:171–226. doi: 10.1016/b978-0-12-039232-2.50011-6. [DOI] [PubMed] [Google Scholar]
- Geller S. A., Muller R., Greenberg M. L., Siegal F. P. Acquired immunodeficiency syndrome. Distinctive features of bone marrow biopsies. Arch Pathol Lab Med. 1985 Feb;109(2):138–141. [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. Pathogenesis of lentivirus infections. Nature. 1986 Jul 10;322(6075):130–136. doi: 10.1038/322130a0. [DOI] [PubMed] [Google Scholar]
- Heidecker G., Lerche N. W., Lowenstine L. J., Lackner A. A., Osborn K. G., Gardner M. B., Marx P. A. Induction of simian acquired immune deficiency syndrome (SAIDS) with a molecular clone of a type D SAIDS retrovirus. J Virol. 1987 Oct;61(10):3066–3071. doi: 10.1128/jvi.61.10.3066-3071.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoffman A. D., Banapour B., Levy J. A. Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions. Virology. 1985 Dec;147(2):326–335. doi: 10.1016/0042-6822(85)90135-7. [DOI] [PubMed] [Google Scholar]
- Leiderman I. Z., Greenberg M. L., Adelsberg B. R., Siegal F. P. A glycoprotein inhibitor of in vitro granulopoiesis associated with AIDS. Blood. 1987 Nov;70(5):1267–1272. [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]
- Levy J. A. Human immunodeficiency viruses and the pathogenesis of AIDS. JAMA. 1989 May 26;261(20):2997–3006. [PubMed] [Google Scholar]
- Lowenstine L. J., Pedersen N. C., Higgins J., Pallis K. C., Uyeda A., Marx P., Lerche N. W., Munn R. J., Gardner M. B. Seroepidemiologic survey of captive Old-World primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys). Int J Cancer. 1986 Oct 15;38(4):563–574. doi: 10.1002/ijc.2910380417. [DOI] [PubMed] [Google Scholar]
- Lowenstine L. J., Pedersen N. C., Higgins J., Pallis K. C., Uyeda A., Marx P., Lerche N. W., Munn R. J., Gardner M. B. Seroepidemiologic survey of captive Old-World primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys). Int J Cancer. 1986 Oct 15;38(4):563–574. doi: 10.1002/ijc.2910380417. [DOI] [PubMed] [Google Scholar]
- Lunardi-Iskandar Y., Nugeyre M. T., Georgoulias V., Barré-Sinoussi F., Jasmin C., Chermann J. C. Replication of the human immunodeficiency virus 1 and impaired differentiation of T cells after in vitro infection of bone marrow immature T cells. J Clin Invest. 1989 Feb;83(2):610–615. doi: 10.1172/JCI113924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacKenzie M., Lowenstine L., Lalchandani R., Lerche N., Osborn K., Spinner A., Bleviss M., Hendrickson R., Gardner M. Hematologic abnormalities in simian acquired immune deficiency syndrome. Lab Anim Sci. 1986 Feb;36(1):14–19. [PubMed] [Google Scholar]
- McElrath M. J., Pruett J. E., Cohn Z. A. Mononuclear phagocytes of blood and bone marrow: comparative roles as viral reservoirs in human immunodeficiency virus type 1 infections. Proc Natl Acad Sci U S A. 1989 Jan;86(2):675–679. doi: 10.1073/pnas.86.2.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mullins J. I., Chen C. S., Hoover E. A. Disease-specific and tissue-specific production of unintegrated feline leukaemia virus variant DNA in feline AIDS. Nature. 1986 Jan 23;319(6051):333–336. doi: 10.1038/319333a0. [DOI] [PubMed] [Google Scholar]
- Murphey-Corb M., Martin L. N., Rangan S. R., Baskin G. B., Gormus B. J., Wolf R. H., Andes W. A., West M., Montelaro R. C. Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature. 1986 May 22;321(6068):435–437. doi: 10.1038/321435a0. [DOI] [PubMed] [Google Scholar]
- Narayan O., Wolinsky J. S., Clements J. E., Strandberg J. D., Griffin D. E., Cork L. C. Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats. J Gen Virol. 1982 Apr;59(Pt 2):345–356. doi: 10.1099/0022-1317-59-2-345. [DOI] [PubMed] [Google Scholar]
- Osborne B. M., Guarda L. A., Butler J. J. Bone marrow biopsies in patients with the acquired immunodeficiency syndrome. Hum Pathol. 1984 Nov;15(11):1048–1053. doi: 10.1016/s0046-8177(84)80248-8. [DOI] [PubMed] [Google Scholar]
- Pedersen N. C., Torten M., Rideout B., Sparger E., Tonachini T., Luciw P. A., Ackley C., Levy N., Yamamoto J. Feline leukemia virus infection as a potentiating cofactor for the primary and secondary stages of experimentally induced feline immunodeficiency virus infection. J Virol. 1990 Feb;64(2):598–606. doi: 10.1128/jvi.64.2.598-606.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perkocha L. A., Rodgers G. M. Hematologic aspects of human immunodeficiency virus infection: laboratory and clinical considerations. Am J Hematol. 1988 Oct;29(2):94–105. doi: 10.1002/ajh.2830290207. [DOI] [PubMed] [Google Scholar]
- Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [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]
- Schneider D. R., Picker L. J. Myelodysplasia in the acquired immune deficiency syndrome. Am J Clin Pathol. 1985 Aug;84(2):144–152. doi: 10.1093/ajcp/84.2.144. [DOI] [PubMed] [Google Scholar]
- Stella C. C., Ganser A., Hoelzer D. Defective in vitro growth of the hemopoietic progenitor cells in the acquired immunodeficiency syndrome. J Clin Invest. 1987 Aug;80(2):286–293. doi: 10.1172/JCI113071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutjipto S., Kodama T., Yee J., Gettie A., Jennings M., Desrosiers R. C., Marx P. A. Characterization of monoclonal antibodies that distinguish simian immunodeficiency virus isolates from each other and from human immunodeficiency virus types 1 and 2. J Gen Virol. 1990 Jan;71(Pt 1):247–249. doi: 10.1099/0022-1317-71-1-247. [DOI] [PubMed] [Google Scholar]
- Sutjipto S., Pedersen N. C., Miller C. J., Gardner M. B., Hanson C. V., Gettie A., Jennings M., Higgins J., Marx P. A. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals. J Virol. 1990 May;64(5):2290–2297. doi: 10.1128/jvi.64.5.2290-2297.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Treacy M., Lai L., Costello C., Clark A. Peripheral blood and bone marrow abnormalities in patients with HIV related disease. Br J Haematol. 1987 Mar;65(3):289–294. doi: 10.1111/j.1365-2141.1987.tb06855.x. [DOI] [PubMed] [Google Scholar]
- Watanabe M., Ringler D. J., Nakamura M., DeLong P. A., Letvin N. L. Simian immunodeficiency virus inhibits bone marrow hematopoietic progenitor cell growth. J Virol. 1990 Feb;64(2):656–663. doi: 10.1128/jvi.64.2.656-663.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zon L. I., Arkin C., Groopman J. E. Haematologic manifestations of the human immune deficiency virus (HIV). Br J Haematol. 1987 Jun;66(2):251–256. doi: 10.1111/j.1365-2141.1987.tb01307.x. [DOI] [PubMed] [Google Scholar]
- Zucker-Franklin D., Cao Y. Z. Megakaryocytes of human immunodeficiency virus-infected individuals express viral RNA. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5595–5599. doi: 10.1073/pnas.86.14.5595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zucker-Franklin D., Termin C. S., Cooper M. C. Structural changes in the megakaryocytes of patients infected with the human immune deficiency virus (HIV-1). Am J Pathol. 1989 Jun;134(6):1295–1303. [PMC free article] [PubMed] [Google Scholar]




