Absent or Rare Human Immunodeficiency Virus Infection of Bone Marrow Stem/progenitor Cells in Vivo

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1991 Apr 1

PMID 2002553

Citations 29

Authors

B R Davis

D H Schwartz

J C Marx

C E Johnson

J M Berry

J Lyding

T C Merigan

A Zander

Affiliations

Soon will be listed here.

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.

Citing Articles

Consequences of HIV infection in the bone marrow niche.

Herd C, Mellet J, Mashingaidze T, Durandt C, Pepper M Front Immunol. 2023; 14:1163012.

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P2X7 Receptor Inhibition Improves CD34 T-Cell Differentiation in HIV-Infected Immunological Nonresponders on c-ART.

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HIV/AIDS: modified stem cells in the spotlight.

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Effects of human immunodeficiency virus on the erythrocyte and megakaryocyte lineages.

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References

Civin C, Strauss L, Brovall C, Fackler M, Schwartz J, Shaper J . Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984; 133(1):157-65. View

Molina J, Scadden D, Sakaguchi M, Fuller B, Woon A, Groopman J . 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; 76(12):2476-82. View

Andrews R, Singer J, Bernstein I . Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors. Blood. 1986; 67(3):842-5. View

Folks T, Powell D, Lightfoote M, Koenig S, Fauci A, Benn S . Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med. 1986; 164(1):280-90. PMC: 2188205. DOI: 10.1084/jem.164.1.280. View

Scharf S, Horn G, Erlich H . Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science. 1986; 233(4768):1076-8. DOI: 10.1126/science.3461561. View

Donahue R, Johnson M, Zon L, Clark S, Groopman J . Suppression of in vitro haematopoiesis following human immunodeficiency virus infection. Nature. 1987; 326(6109):200-3. DOI: 10.1038/326200a0. View

Zon L, Arkin C, Groopman J . Haematologic manifestations of the human immune deficiency virus (HIV). Br J Haematol. 1987; 66(2):251-6. DOI: 10.1111/j.1365-2141.1987.tb01307.x. View

Stella C, Ganser A, Hoelzer D . Defective in vitro growth of the hemopoietic progenitor cells in the acquired immunodeficiency syndrome. J Clin Invest. 1987; 80(2):286-93. PMC: 442236. DOI: 10.1172/JCI113071. View

Ou C, Kwok S, Mitchell S, Mack D, Sninsky J, Krebs J . DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988; 239(4837):295-7. DOI: 10.1126/science.3336784. View

10.

Fauci A . The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988; 239(4840):617-22. DOI: 10.1126/science.3277274. View

11.

Berenson R, Andrews R, Bensinger W, Kalamasz D, Knitter G, Buckner C . Antigen CD34+ marrow cells engraft lethally irradiated baboons. J Clin Invest. 1988; 81(3):951-5. PMC: 442551. DOI: 10.1172/JCI113409. View

12.

Baltimore D . Gene therapy. Intracellular immunization. Nature. 1988; 335(6189):395-6. DOI: 10.1038/335395a0. View

13.

Folks T, Kessler S, Orenstein J, Justement J, Jaffe E, Fauci A . Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow. Science. 1988; 242(4880):919-22. DOI: 10.1126/science.2460922. View

14.

McElrath M, PRUETT J, COHN Z . 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; 86(2):675-9. PMC: 286536. DOI: 10.1073/pnas.86.2.675. View

15.

Andrews R, Singer J, Bernstein I . 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; 169(5):1721-31. PMC: 2189320. DOI: 10.1084/jem.169.5.1721. View

16.

Schnittman S, Psallidopoulos M, Lane H, Thompson L, Baseler M, Massari F . The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science. 1989; 245(4915):305-8. DOI: 10.1126/science.2665081. View

17.

Sutherland H, Eaves C, Eaves A, Dragowska W, Lansdorp P . Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood. 1989; 74(5):1563-70. View

18.

Psallidopoulos M, Schnittman S, Thompson 3rd L, Baseler M, Fauci A, Lane H . Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals. J Virol. 1989; 63(11):4626-31. PMC: 251096. DOI: 10.1128/JVI.63.11.4626-4631.1989. View

19.

Ho D, Moudgil T, Alam M . Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989; 321(24):1621-5. DOI: 10.1056/NEJM198912143212401. View

20.

Holland H, Saral R, Rossi J, Donnenberg A, BURNS W, Beschorner W . 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; 111(12):973-81. DOI: 10.7326/0003-4819-111-12-973. View