Effects of HIV Type 1 Infection on Hematopoiesis in Botswana

Redd, Andrew D.; Avalos, Ava; Phiri, Kelesitse; Essex, Max

doi:10.1089/aid.2006.0283

Cited by 6 publications

(13 citation statements)

References 26 publications

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“…[2][3][4] Recent findings by our group demonstrated that HIV-1 infection was directly associated with hematopoiesis in HIV-infected patients in Botswana, a country in southern Africa. 5 The study found direct positive associations between CD4 ϩ and CD34 ϩ cell levels, and between CD34 ϩ /CD4 ϩ dual-positive cell levels and both hemoglobin counts and colony-forming ability, as well as negative correlations between circulating viral levels and all indicators of HIV infection and hematopoietic health tested. 5 These results suggested a direct role for HIV-1C in the hematopoietic process that was not due to host population differences.…”

Section: Introductionmentioning

confidence: 77%

“…5 The study found direct positive associations between CD4 ϩ and CD34 ϩ cell levels, and between CD34 ϩ /CD4 ϩ dual-positive cell levels and both hemoglobin counts and colony-forming ability, as well as negative correlations between circulating viral levels and all indicators of HIV infection and hematopoietic health tested. 5 These results suggested a direct role for HIV-1C in the hematopoietic process that was not due to host population differences. We theorized that these associations, as well as the increased anemia rates seen in southern Africa, were related to an expansion of the cell tropism of HIV-1C to infect hematopoietic progenitor cells (HPCs).…”

Section: Introductionmentioning

confidence: 77%

“…5 All participants provided written informed consent and all study procedures were approved by the institutional review boards at the Ministry of Health of the Republic of Botswana and the Harvard School of Public Health. Each patient had one 10-mL tube of blood taken in a heparin tube.…”

Section: In Vivo Analysismentioning

confidence: 99%

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Infection of hematopoietic progenitor cells by HIV-1 subtype C, and its association with anemia in southern Africa

Redd

Avalos²,

Essex

2007

Blood

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Reports from southern Africa, an area in which human immunodeficiency virus type 1 (HIV-1) infection is caused almost exclusively by subtype C (HIV-1C), have shown increased rates of anemia in HIV-infected populations compared with similar acquired immunodeficiency syndrome (AIDS) patients in the United States, an area predominantly infected with subtype B (HIV-1B). Recent findings by our group demonstrated a direct association between HIV-1 infection and hematopoietic progenitor cell health in Botswana. Therefore, using a single-colony infection assay and quantitative proviral analysis, we examined whether HIV-1C could infect hematopoietic progenitor cells (HPCs) and whether this phenotype was associated with the higher rates of anemia found in southern Africa. The results show that a significant number of HIV-1C, but not HIV-1B, isolates can infect HPCs in vitro (P < .05). In addition, a portion of HIV-1C–positive Africans had infected progenitor cell populations in vivo, which was associated with higher rates of anemia in these patients (P < .05). This represents a difference in cell tropism between 2 geographically separate and distinct HIV-1 subtypes. The association of this hematotropic phenotype with higher rates of anemia should be considered when examining anti-HIV drug treatment regimens in HIV-1C–predominant areas, such as southern Africa.

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Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 77%

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Infection of hematopoietic progenitor cells by HIV-1 subtype C, and its association with anemia in southern Africa

Redd

Avalos²,

Essex

2007

Blood

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“…A negative correlation between circulating viral levels and density of colony forming ability, as well as an association between HPC infection and anemia, has been shown in HIV-1C-infected subjects. 2 This suggests that HIV-1 infection of HPCs can affect hematopoiesis and colonyforming ability. The observance of no correlation between circulating viral level and density of colony formation in our population further supports our conclusion that HIV-1A and HIV-1D do not preferentially infect HPCs over mature HIV target cells in vivo.…”

Section: Mullis Et Almentioning

confidence: 99%

“…1 The ability of HIV-1 to infect these hematopoietic progenitor cells (HPCs) has been investigated as a potential cause of the many hematopoietic abnormalities observed in infected individuals. [2][3][4][5] HIV-1 has been detected in a variety of hematopoietic progenitor cell types suggesting that HIV-1 is capable of infecting HPCs. 3,4,6,7 However, other studies have not detected HIV-1 infection in HPCs leading to questions about the relevance and extent of HPC infection in vivo.…”

mentioning

confidence: 99%

Short Communication: Colony-Forming Hematopoietic Progenitor Cells Are Not Preferentially Infected by HIV Type 1 Subtypes A and Din Vivo

Mullis

Oliver

Eller³

et al. 2012

AIDS Research and Human Retroviruses

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HIV subtype C has previously been shown to infect hematopoietic progenitor cells (HPCs) at a significantly higher rate than subtype B. To better understand the subtype-specific nature of HPC infection, we examined the prevalence of HPC infection in vivo by HIV-1 subtypes A and D. HIV-1 infection of HPC was examined in 40 individuals, 19 infected with subtype A and 21 with subtype D, using a single colony assay format. DNA from 1177 extracted colonies was tested for integrated viral DNA of the p24 gene. Four colonies were found to be stably infected, three of 462 colonies (0.65%) from HIV-1A-infected individuals (1/19 individuals) and one of 715 colonies (0.14%) from HIV-1D-infected individuals (1/22 individuals). These rates of colony infection were comparable to the rates observed in PBMCs from the same subjects. Additionally, no correlation was observed between cell colony density and circulating viral load or proviral load. Our findings suggest that HIV-1 subtypes A and D do not preferentially infect colony-forming HPCs over mature HIV target cells in vivo.

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Hematopoietic stem/precursor cells as HIV reservoirs

McNamara

Collins

2011

Current Opinion in HIV and AIDS

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Purpose of Review Although latent HIV-1 infection in CD4+ T cells contributes to HIV persistence, there is mounting evidence that other viral reservoirs exist. Here, we review recent data suggesting that the infection of hematopoietic progenitor cells creates additional reservoirs for HIV in vivo. Recent Findings New studies suggest that some types of hematopoietic progenitor cells have the potential to generate reservoirs for HIV. This review focuses on two types that can be infected by HIV in vitro and in vivo: multipotent hematopoietic progenitor cells in the bone marrow and circulating mast cell progenitors. Of these two types, only CD34+ bone marrow cells have been shown to harbor latent provirus in HIV+ individuals with undetectable viral loads on HAART. Latent infection of these long-lived cell types may create a significant barrier to HIV eradication; indeed the potential infection of hematopoietic stem cells in particular could lead to an HIV reservoir that does not appreciably decay over the lifespan of the host. Summary To eradicate HIV infection, it will be necessary to purge all viral reservoirs in the host. The findings highlighted here suggest that multipotent hematopoietic progenitor cells and possibly tissue mast cells may constitute significant reservoirs for HIV that must be addressed in order to eliminate HIV infection. Future studies are needed to determine which types of CD34+ cells are infected in vivo and whether infected CD34+ cells contribute to residual viremia in people with undetectable viral loads on HAART.

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Effects of HIV Type 1 Infection on Hematopoiesis in Botswana

Cited by 6 publications

References 26 publications

Infection of hematopoietic progenitor cells by HIV-1 subtype C, and its association with anemia in southern Africa

Infection of hematopoietic progenitor cells by HIV-1 subtype C, and its association with anemia in southern Africa

Short Communication: Colony-Forming Hematopoietic Progenitor Cells Are Not Preferentially Infected by HIV Type 1 Subtypes A and Din Vivo

Hematopoietic stem/precursor cells as HIV reservoirs

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