Effect of Human Immunodeficiency Virus Type 1 on CD34+Cells (original) (raw)
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AIDS Research and Human Retroviruses, 2000
The mechanisms responsible for the hematopoietic failure in human immunodeficiency virus type 1 (HIV-1)-infected patients are still unknown. Several findings indicate that the in vitro proliferative potential of precursor cells from AIDS patients is reduced. The changes seen in bone marrow (BM) morphology and the defective BM functions associated with cytopenias have both been proposed as potential explanations. In patients treated with highly active antiretroviral therapy (HAART) an immune reconstitution associated with increased whole blood cell counts has been described. We have investigated the effects of HAART on the number of colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs), using long-term BM cell cultures (LTBMC) in a group of subjects with HIV-1 infection enrolled in an open study to evaluate the mechanisms of immune reconstitution during HAART. In each patient, the increase in colony growth was homogeneous, regardless of the type of hematopoietic progenitor cells assayed; in four subjects an increase in the most primitive progenitor cells (LTC-ICs) was observed. These findings were associated with the in vivo data showing increased numbers of BM mononuclear cells (BMMCs) after HAART and with a rise in peripheral CD4(+) T cell counts and decreased levels of plasma HIV-1 RNA. A decreased number of hematopoietic progenitor cells and/or a defective modulation of progenitor cell growth might be the cause of the hematological abnormalities in AIDS patients. Controlling HIV-1 replication by HAART could determine a restoration of stem cell activity, probably because of the suppression of factors that inhibit normal hematopoiesis.
Loss of primitive hematopoietic progenitors in patients with human immunodeficiency virus infection
Blood, 1996
A number of hematologic abnormalities, including cytopenias, have been observed in patients with human immunodeficiency virus (HIV) infection. To elucidate their mechanisms, primitive cells from bone marrow aspirates of 21 patients with HIV-1 infection were quantitated by flow cytometry. The mean percentage of CD34+ cells is not significantly altered in HIV-1-infected patients in comparison with HIV-1-seronegative controls. In contrast, two- and three-color immunofluorescence analysis showed that in all HIV-1 samples, most CD34+ cells coexpressed the CD38 antigen. The proportion of HIV-1-derived CD34+ cells that did not express the CD38 antigen was significantly lower (HIV-1+: mean, 1.73%; controls: mean, 14%; P < .0005) than in controls. Moreover, of Thy-1+ cells, the proportion of CD34+ cells was twofold lower in HIV-1-infected patients (HIV-1+: mean, 12%; controls, 25%, P < .0005), which suggests that phenotypically primitive cells are depleted in HIV-1 infection. In vitro ...
Running title: HIV1C Infection of Hematopoietic Progenitor Cells
2007
Reports from southern Africa, an area in which HIV-1 infection is caused almost exclusively by subtype C (HIV-1C), have shown increased rates of anemia in HIVinfected populations when compared to similar AIDS patients in the U.S., 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 (HPC) 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 HPC in vitro (P < 0.05). In addition, a portion of HIV-1C positive Africans had infected progenitor cell populations in vivo, which associated with higher rates of anemia in these patients (P < 0.05). This represents a difference in cell tropism between two 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.
Hematological Changes in HIV Infection
In patients with human immunodeficiency virus (HIV), anaemia, leukopenia and thrombocytopenia are the commonest hematological abnormalities found. These abnormalities present opportunity for further complications to arise. This review looks into the numerous hematological changes, their aetiology, other complicating factors and some treatment options for the various hematological problems as a means to improve quality of life of patients living with HIV.
CD34' Hematopoietic Progenitor Cells Are Not a Major Reservoir of the Human Immunodeficiency Virus
EMATOLOGIC ABNORMALITIES are frequent in H patients with late-stage infection with the human immunodeficiency virus- 1 (HIV- l).'.' Cytopenias of all blood cells are often accompanied by marked changes of bone marrow morphology.' The cytologic pattern varies but is similar to that observed in patients with myelodysplastic ~yndrome.~.~ It has been argued that the hematologic abnormalities in acquired immunodeficiency syndrome (AIDS) are the result of the infection of the bone marrow cells with HIV-1. Virus-specific RNA could be detected by in situ hybridiza- tion in megakaryocytes from 10 of 10 thrombocytopenic patients with AIDS as well as in myelocytes and mono- myelocytes.6 In addition, p24-protein was found in denuded megakaryocyte-like cells.' Monocytes/macrophages are also infected with HIV.' However, recent reports show that they do not serve as a major virus reservoir?-" Several findings indicate that hematopoietic precursor cells in the bone mar...
Experimental Cell Research, 1999
Apoptosis plays a major role during HIV infection, including the primary, acute HIV syndrome (AHS), during which such phenomenon is massive. We asked whether apoptosis involved not only peripheral blood lymphocytes, but also monocytes (PBM) and granulocytes (PBG). Thus, we studied cells from different patients during the acute phase of the viral syndrome. The CD95 molecule was expressed at high density on the PBM and PBG surface during AHS. Culturing PBG for a few hours resulted in a significant membrane expression of phosphatidylserine, consistent with apoptosis. However, cells maintained for hours plasma membrane integrity and showed no relevant changes in mitochondrial membrane potential. The overexpression of CD95 was not associated with high plasmatic levels of sCD95 and, together with apoptosis and its related markers decreased after a few weeks of highly active antiretroviral therapy. During AHS, a deregulation of the CD95 system occurs in monocytes and granulocytes, is related to a high propensity of PBG to undergo apoptosis, and may contribute to the pathogenesis of the disease. Antiretroviral treatment resulted not only in a decrease of virus production, but also in a reduced PBG tendency to undergo spontaneous apoptosis. Even if the mechanism(s) responsible for this phenomenon remains to be elucidated, our data suggest a possible (indirect?) action of antiretroviral therapies on PBG and PBM which could explain, at least partially, the rescue of natural immunity and the reduced use of granulocyte-colony stimulating factor during such treatments.