Comparison of CD4+ T cell function between HIV-1 resistant and HIV-1 susceptible individuals (Immune)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Paul McLaren
PROVIDER: E-GEOD-14279 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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:Understanding why some indidivual resist HIV-1 infection despite continued exposure is an important goal for vaccine development. We compared CD4+ T cell gene expression at baseline and after antigenic stimulation in HIV-1 resistant commercial sex-workers from Nairobi, Kenya to HIV-1 low-risk negative (non-resistant) non-commercial sex-workers using immune-focused gene expression arrays Keywords: Case-control, disease state analysis
2010-03-02 | GSE14279 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE14278: Comparison of CD4+ T cell function between HIV-1 resistant and HIV-1 susceptible individuals (Affymetrix) GSE14279: Comparison of CD4+ T cell function between HIV-1 resistant and HIV-1 susceptible individuals (Immune) Refer to individual Series
2010-05-07 | E-GEOD-14280 | biostudies-arrayexpress
Project description:Understanding why some indidivual 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 Keywords: Case-control, disease state analysis
2010-03-02 | GSE14278 | GEO
Project description:We carried out a global whole blood genome wide expression profiling of HIV exposed and uninfected women from Nairobi to identify host factors which may be a key contribution to HIV resistance phenomenon. To identify novel biomarkers for HIV resistance including pathways that may be critical in anti-HIV vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV Exposed and uninfected volunteers from a commercial sex worker cohort in Nairobi and compared their profiles to HIV susceptible negative controls. Whole blood samples were collected from 43 HIV resistant and a similar number of HIV negative antenatal clinic attendees and total RNA extracted and hybridized to the affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). More than 2,274 probe sets were differentially expressed in the HIV resistant women as compared to the control group (fold change ≥1.3; p value ≤ 0.0001, FDR <0.05) . Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished EUs from susceptible controls. Pathway analysis of the differentially expressed genes through the KEGG signaling revealed a majority of the impacted pathways (13 of 15, 87%) were significantly down expressed. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, Phosphatidyl inositol, Natural Killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up expressed. We infer that the hallmark of HIV resistance is down regulation of genes in key signaling pathways that HIV depends on for infection and suggest that an anti-HIV vaccine design may need to incorporate components that switch down specific immune activating factors.
2012-11-11 | GSE33580 | GEO
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:<p>Rare individuals are highly resistant to infection with human immunodeficiency virus (HIV). Studies of candidate genes resulted in the discovery of a 32bp deletion in the CC-chemokine receptor 5 gene (CCR5Δ32), which rendered this critical co-receptor for primary HIV infection to be non-functional. Pharmacologic and vaccine-induced blockade of CCR5 is being pursued to treat and prevent HIV infection and other conditions.</p> <p>The allele frequency of CCR5Δ32 among persons of European ancestry is approximately 10%. CCR5Δ32/Δ32 homozygotes are almost totally resistant to HIV infection. People with severe hemophilia A require frequent replacement with clotting Factor VIII (FVIII) to control hemorrhage. Prior to the discovery of HIV in 1984 and licensure of recombinant FVIII in the late 1980s, people with severe hemophilia A were treated with plasma-derived FVIII and thus were intensively exposed to HIV. Only 5% of such patients were not infected with HIV. Of these, approximately 1/3 were CCR5Δ32/Δ32 homozygotes. The remaining 2/3 of these people who were highly resistant to HIV remain unexplained. This project seeks to discover genome variations among people who are highly resistant to HIV infection. Such variation is likely to serve as a target for reducing the morbidity and incidence of HIV. </p>
| phs000445.v1.p1 | EGA
Project description:This SuperSeries is composed of the following subset Series: GSE22768: Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vivo analysis GSE22769: Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vitro analysis To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity. Refer to individual Series
2012-11-20 | E-GEOD-22822 | biostudies-arrayexpress
Project description:Host directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Since HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1 infected patients with paired samples on and off antiretroviral treatment. In the in vitro experiment, the proteome of CD4+ T cells was quantified over a time course following HIV-1 infection. 1,725 host cell proteins and 4 HIV-1 proteins were quantified, with 145 proteins changing significantly during the time course. Changes in the proteome peaked 24 hours after infection, concomitantly with significant HIV-1 protein production. In the in vivo branch of the study, CD4+ T cells from viremic patients and those with no detectable viral load after treatment were sorted and the proteomes quantified. We consistently detected 895 proteins, 172 of which were considered to be significantly different between viraemic patients and patients undergoing successful treatment. The proteome of in vitro infected CD4+ T cells was modulated on multiple functional levels, including TLR-4 signalling and the type 1 interferon signalling pathway. Perturbations in the type 1 interferon signalling pathway were recapitulated in CD4+ T cells from patients. The study shows that proteome maps generated by SWATH-MS indicate a range of functionally significant changes in the proteome of HIV infected human CD4+ T cells. Exploring these perturbations in more detail may help identify new targets for immune based interventions.
2017-02-28 | PXD005234 | Pride