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. 1991 Apr;65(4):1985–1990. doi: 10.1128/jvi.65.4.1985-1990.1991

Absent or rare human immunodeficiency virus infection of bone marrow stem/progenitor cells in vivo.

B R Davis 1, D H Schwartz 1, J C Marx 1, C E Johnson 1, J M Berry 1, J Lyding 1, T C Merigan 1, A Zander 1
PMCID: PMC240035  PMID: 2002553

Abstract

An important question in human immunodeficiency virus (HIV) pathogenesis is whether HIV-infected bone marrow CD34+ stem/progenitor cells serve as a significant reservoir of virus in HIV-infected individuals. Our data indicate that infection of bone marrow stem/progenitor cells with HIV occurs rarely, if ever, in vivo. In the present study, CD34+ cells were immunomagnetically purified from the bone marrow of HIV-seropositive individuals, and purified cells or colony-forming cells of the granulocyte/macrophage lineage were analyzed for HIV proviral DNA by the polymerase chain reaction. No HIV DNA was detected in colony-forming cells of the granulocyte/macrophage lineage from HIV-positive patients. Furthermore, no virus was found in CD34(+)-enriched cells from six of seven samples from asymptomatic HIV-infected individuals and four of four samples from patients with AIDS-related complex or AIDS. Thus, infected stem cells are not a major source of persistent HIV and do not account for hematopoietic suppression. These findings have positive implications for the concept of marrow reconstitution with autologous stem cells, genetically engineered for HIV resistance, following marrow-ablative antiviral therapy.

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Selected References

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  1. Andrews R. G., Singer J. W., Bernstein I. D. Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors. Blood. 1986 Mar;67(3):842–845. [PubMed] [Google Scholar]
  2. Andrews R. G., Singer J. W., Bernstein I. D. Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties. J Exp Med. 1989 May 1;169(5):1721–1731. doi: 10.1084/jem.169.5.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baltimore D. Gene therapy. Intracellular immunization. Nature. 1988 Sep 29;335(6189):395–396. doi: 10.1038/335395a0. [DOI] [PubMed] [Google Scholar]
  4. Berenson R. J., Andrews R. G., Bensinger W. I., Kalamasz D., Knitter G., Buckner C. D., Bernstein I. D. Antigen CD34+ marrow cells engraft lethally irradiated baboons. J Clin Invest. 1988 Mar;81(3):951–955. doi: 10.1172/JCI113409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buonocore L., Rose J. K. Prevention of HIV-1 glycoprotein transport by soluble CD4 retained in the endoplasmic reticulum. Nature. 1990 Jun 14;345(6276):625–628. doi: 10.1038/345625a0. [DOI] [PubMed] [Google Scholar]
  6. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  7. 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]
  8. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Folks T. M., Powell D., Lightfoote M., Koenig S., Fauci A. S., Benn S., Rabson A., Daugherty D., Gendelman H. E., Hoggan M. D. Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med. 1986 Jul 1;164(1):280–290. doi: 10.1084/jem.164.1.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Folks T., Benn S., Rabson A., Theodore T., Hoggan M. D., Martin M., Lightfoote M., Sell K. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539–4543. doi: 10.1073/pnas.82.13.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
  13. Holland H. K., Saral R., Rossi J. J., Donnenberg A. D., Burns W. H., Beschorner W. E., Farzadegan H., Jones R. J., Quinnan G. V., Vogelsang G. B. Allogeneic bone marrow transplantation, zidovudine, and human immunodeficiency virus type 1 (HIV-1) infection. Studies in a patient with non-Hodgkin lymphoma. Ann Intern Med. 1989 Dec 15;111(12):973–981. doi: 10.7326/0003-4819-111-12-973. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Molina J. M., Scadden D. T., Sakaguchi M., Fuller B., Woon A., Groopman J. E. Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus. Blood. 1990 Dec 15;76(12):2476–2482. [PubMed] [Google Scholar]
  16. 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]
  17. Psallidopoulos M. C., Schnittman S. M., Thompson L. M., 3rd, Baseler M., Fauci A. S., Lane H. C., Salzman N. P. Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals. J Virol. 1989 Nov;63(11):4626–4631. doi: 10.1128/jvi.63.11.4626-4631.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Scharf S. J., Horn G. T., Erlich H. A. Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science. 1986 Sep 5;233(4768):1076–1078. doi: 10.1126/science.3461561. [DOI] [PubMed] [Google Scholar]
  19. Schnittman S. M., Psallidopoulos M. C., Lane H. C., Thompson L., Baseler M., Massari F., Fox C. H., Salzman N. P., Fauci A. S. The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science. 1989 Jul 21;245(4915):305–308. doi: 10.1126/science.2665081. [DOI] [PubMed] [Google Scholar]
  20. Simmonds P., Balfe P., Peutherer J. F., Ludlam C. A., Bishop J. O., Brown A. J. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol. 1990 Feb;64(2):864–872. doi: 10.1128/jvi.64.2.864-872.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Sutherland H. J., Eaves C. J., Eaves A. C., Dragowska W., Lansdorp P. M. Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood. 1989 Oct;74(5):1563–1570. [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. von Laer D., Hufert F. T., Fenner T. E., Schwander S., Dietrich M., Schmitz H., Kern P. CD34+ hematopoietic progenitor cells are not a major reservoir of the human immunodeficiency virus. Blood. 1990 Oct 1;76(7):1281–1286. [PubMed] [Google Scholar]

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