Comparison of CD4+ T cell function between HIV-1 resistant and HIV-1 susceptible individuals
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Paul McLaren
PROVIDER: E-GEOD-14280 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Understanding why some individual resist HIV-1 infection despite continued exposure is an important goal for vaccine development. We compared CD4+ T cell gene expression at baseline in HIV-1 resistant commercial sex-workers from Nairobi, Kenya to HIV-1 high-risk negative (non-resistant) commercial sex-workers using gene expression arrays Experiment Overall Design: CD4+ T cells from both HIV resistant and HIV low-risk negative individuals were isolated from PBMC after 24 hours of culture by negative selection. Total RNA was isolated and gene expression compared using Affymetrix total genome arrays.
2009-01-17 | E-GEOD-14278 | biostudies-arrayexpress
Project description:HIV-related fatigue is multi-causal in origin and potentially related to mitochondrial dysfunction caused by toxicity from nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral therapy. CD14+ cells are undifferentiated macrophages, vulnerable to HIV infection, and easily accessible for gene expression experiments in a purified cell population. We utilized a novel mitochondrially-specific gene expression microarray to assess mitochondrial and nuclear genes in CD14+ cells of low- and high-fatigued, NRTI-treated HIV/AIDS patients (n=5 each). Novel Bayesian and liquid association network methods identified 33 genes predictive of low versus high fatigue and 32 genes predictive of healthy versus HIV infection. Sulfotransferase 2B1 (SULT2B1) is relevant to both the cholesterol and testosterone pathway, and like several inner mitochondrial membrane genes also identified, predictive of fatigue status, while outer mitochondrial membrane genes were predictive of HIV status. A surprising finding was that adenylate cyclase 2 (ADCY2) was a predictor of both HIV and fatigue; it had the highest Kendallâs Tau association value in the HIV group, but in reverse, the lowest Tau value in the fatigue group. Assaying CD14+ cells may provide an alternative to muscle biopsy and a minimally invasive procedure to evaluate patient mitochondrial function, and Bayesian and network tools are useful to identify the link between subjective symptom perceptions and underlying biologically pathways. Fatigue status in HIV patients treated with NRTIs was found to be linked to RNA expression differences related to mitochondrial function. Additional studies are needed to confirm the relevance of our findings in CD14+ cells in other tissues (e. g. skeletal muscle) and to understand the significance of key genes such as SULT2B and ADCY2 in fatigue and HIV disease. The design was a comparison of HIV high fatigue to HIV low fatigue. Low fatigue was determined as 3-7 on the Revised Piper Fatigue Score and High fatigue was a score of 7 or greater. Five HIV negative control samples were used to compare normal fatigue and non-disease status.
2010-06-21 | E-GEOD-18468 | biostudies-arrayexpress
Project description:Mechanisms that may allow circulating monocytes to persist as CD4 T cells diminish in HIV-1 infection have not been investigated. We have characterized steady-state gene expression signatures in circulating monocytes from HIV-infected subjects and have identified a stable anti-apoptosis gene signature comprised of 38 genes associated with p53, CD40L, TNF and MAPKinase signaling networks. The significance of this gene signature is indicated by our demonstration of cadmium chloride- or Fas ligand-induced apoptosis resistance in circulating monocytes in contrast to increasing apoptosis in CD4 T cells from the same infected subjects. As potential mechanisms in vivo, we show that monocyte CCR5 binding by HIV-1 virus or agonist chemokines serve as independent viral and host modulators resulting in increased monocyte apoptosis resistance in vitro. We also show evidence for concordance between circulating monocyte apoptosis-related gene expression in HIV-1 infection in vivo and available datasets following viral infection or envelope exposure in monocyte derived macrophages in vitro. The identification of in vivo gene expression associated with monocyte resistance to apoptosis is of relevance to AIDS pathogenesis since it would contribute to: (1) maintaining viability of infection targets and long-term reservoirs of HIV-1 infection in the monocyte/macrophage populations, and (2) protecting a cell subset critical to host survival in spite of sustained high viral replication. Keywords: two group study design 33 samples hybridized, including 13 HIV-1 Patients, 12 Healthy Controls and 4 HIV-1 Patients and 4 Controls followed 6 months later
2010-06-25 | E-GEOD-14542 | biostudies-arrayexpress
Project description:Aanlysis of human resting CD4+T cells and cells activated by two different methods: CD4+ T cells unstimulated (be susceptible but not support to HIV-1) and stimulated either by CD3/CD28 costimulation (reversed susceptibility and resisted to HIV-1) or by PHA/IL-2 for six days (be susceptible and support to HIV-1) to investigate potential mechanism of reversing susceptible to HIV-1. We measured gene expression in resting human CD4+T cells and cells activated by two methods for six days which could induce different effects to HIV-1. Three independent experiments were performed at each treatments using different donors for each experiment.
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