CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1

T. F. Neal, H. K. Holland, C. M. Baum, F. Villinger, A. A. Ansari, R. Saral, J. R. Wingard, William Fleming

Research output: Contribution to journalArticle

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Abstract

Controversy exists as to whether hematopoietic progenitor cells are infected by human immunodeficiency virus-1 (HIV-1) in vivo. Most studies have focused on patients with acquired immunodeficiency syndrome (AIDS)/AIDS- related complex, and little data are available on asymptomatic patients with well preserved CD4+ T-cell counts. To determine if CD34+ hematopoietic progenitor cells are infected early in the course of HIV-1 disease, we evaluated 10 asymptomatic HIV-1 seropositive (HIV-1+) patients. The CD34+ cell fraction was purified by a two-step procedure consisting of both affinity chromatography and fluorescence-activated cell sorting that resulted in a median purity of over 99%. Using conventional and nested polymerase chain reaction (PCR) assays, we evaluated the presence and frequency of HIV- 1 proviral DNA. Both bone marrow mononuclear cells and CD34- cells from all 10 patients were strongly positive for the HIV-1 pol and/or gag gene sequences. In contrast, sorted CD34+ cells from only two of 10 patients were positive, and the number of copies of proviral DNA in these samples was estimated to be from 2 to 5 per 250,000 cells. To test the in vitro functional capacity of CD34+ progenitors, these cells were assayed in both methylcellulose and long-term stromal culture. We found no significant reduction in the number of colony-forming unit-erythroid (CFU-E), burst- forming unit-erythroid (BFU-E), or colony-forming unit-granulocyte macrophage (CFU-GM) colonies, or in the frequency of cobblestone area forming cells from limit dilution analysis in HIV-1+ asymptomatic patients. Pooled methylcellulose colonies generated from CD34+ cells were HIV-1- in nine of 10 samples. All progeny from long-term cultures of CD34+ cells were HIV-1- . We conclude that the CD34+ hematopoietic progenitor compartment is not infected in the majority of asymptomatic HIV-1+ patients, and that these cells may represent a suitable target for strategies designed to protect developing CD4+ T cells from infection.

Original languageEnglish (US)
Pages (from-to)1749-1756
Number of pages8
JournalBlood
Volume86
Issue number5
StatePublished - 1995
Externally publishedYes

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Viruses
HIV-1
Stem Cells
Methylcellulose
T-cells
Erythroid Precursor Cells
Hematopoietic Stem Cells
Acquired Immunodeficiency Syndrome
Affinity chromatography
pol Genes
gag Genes
T-Lymphocytes
Macrophages
Polymerase chain reaction
DNA
Sorting
Virus Diseases
CD4 Lymphocyte Count
Dilution
Affinity Chromatography

ASJC Scopus subject areas

  • Hematology

Cite this

Neal, T. F., Holland, H. K., Baum, C. M., Villinger, F., Ansari, A. A., Saral, R., ... Fleming, W. (1995). CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1. Blood, 86(5), 1749-1756.

CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1. / Neal, T. F.; Holland, H. K.; Baum, C. M.; Villinger, F.; Ansari, A. A.; Saral, R.; Wingard, J. R.; Fleming, William.

In: Blood, Vol. 86, No. 5, 1995, p. 1749-1756.

Research output: Contribution to journalArticle

Neal, TF, Holland, HK, Baum, CM, Villinger, F, Ansari, AA, Saral, R, Wingard, JR & Fleming, W 1995, 'CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1', Blood, vol. 86, no. 5, pp. 1749-1756.
Neal TF, Holland HK, Baum CM, Villinger F, Ansari AA, Saral R et al. CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1. Blood. 1995;86(5):1749-1756.
Neal, T. F. ; Holland, H. K. ; Baum, C. M. ; Villinger, F. ; Ansari, A. A. ; Saral, R. ; Wingard, J. R. ; Fleming, William. / CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1. In: Blood. 1995 ; Vol. 86, No. 5. pp. 1749-1756.
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abstract = "Controversy exists as to whether hematopoietic progenitor cells are infected by human immunodeficiency virus-1 (HIV-1) in vivo. Most studies have focused on patients with acquired immunodeficiency syndrome (AIDS)/AIDS- related complex, and little data are available on asymptomatic patients with well preserved CD4+ T-cell counts. To determine if CD34+ hematopoietic progenitor cells are infected early in the course of HIV-1 disease, we evaluated 10 asymptomatic HIV-1 seropositive (HIV-1+) patients. The CD34+ cell fraction was purified by a two-step procedure consisting of both affinity chromatography and fluorescence-activated cell sorting that resulted in a median purity of over 99{\%}. Using conventional and nested polymerase chain reaction (PCR) assays, we evaluated the presence and frequency of HIV- 1 proviral DNA. Both bone marrow mononuclear cells and CD34- cells from all 10 patients were strongly positive for the HIV-1 pol and/or gag gene sequences. In contrast, sorted CD34+ cells from only two of 10 patients were positive, and the number of copies of proviral DNA in these samples was estimated to be from 2 to 5 per 250,000 cells. To test the in vitro functional capacity of CD34+ progenitors, these cells were assayed in both methylcellulose and long-term stromal culture. We found no significant reduction in the number of colony-forming unit-erythroid (CFU-E), burst- forming unit-erythroid (BFU-E), or colony-forming unit-granulocyte macrophage (CFU-GM) colonies, or in the frequency of cobblestone area forming cells from limit dilution analysis in HIV-1+ asymptomatic patients. Pooled methylcellulose colonies generated from CD34+ cells were HIV-1- in nine of 10 samples. All progeny from long-term cultures of CD34+ cells were HIV-1- . We conclude that the CD34+ hematopoietic progenitor compartment is not infected in the majority of asymptomatic HIV-1+ patients, and that these cells may represent a suitable target for strategies designed to protect developing CD4+ T cells from infection.",
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AU - Holland, H. K.

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AU - Ansari, A. A.

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