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
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.
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 CD4+ T cells from both HIV resistant and HIV low-risk negative individuals were isolated from PBMC after 24 hours of culture by negative slelction. Total RNA was isolated and gene expression compared using immune-focused expression arrays.
Project description:We examined the gene expression profiles in ex vivo human CD4+ and CD8+ T cells from untreated HIV-infected individuals at different clinical stages and rates of disease progression. Profiles of pure CD4+ and CD8+ T cells subsets from HIV-infected nonprogressors who controlled viremia were indistinguishable from HIV-uninfected individuals. Similarly, no gene clusters could distinguish T cells from individuals with early from chronic progressive HIV infection, whereas differences were observed between uninfected or nonprogressors versus early or chronic progressors. In early/chronic HIV infection, three characteristic gene expression signatures were observed: (1) CD4+ and CD8+ T cells showed increased expression of interferon stimulated genes (ISGs). However, some ISGs including CXCL9, CXCL10, and CXCL11, and the IL15R? in both CD4+ and CD8+ T cells and the anti-HIV ISG APOBEC3G in CD4+ T cells, were not upregulated. (2) CD4+ and CD8+ T cells showed a cluster similar to that observed in thymocytes, and (3) more genes were differentially regulated in CD8+ T cells than in CD4+ T cells, including a cluster of genes downregulated exclusively in CD8+ T cells. In conclusion, HIV infection induces a persistent T cell transcriptional profile, early in infection, characterized by a dramatic but potentially aberrant interferon response, and a profile suggesting an active thymic output. We studied a cohort of HIV infected individuals with various clinical stages of HIV infection and healthy uninfected volunteers as a control group (Table 1). We included 5 individuals with early HIV infection (A), five with chronic progressive HIV infection (C), five individuals with non-progressive HIV infection with low or undetectable viral loads (L) and five HIV uninfected individuals (N). The HIV infected individuals were never on therapy prior to entering the study. Samples were taken once from each donor.
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.
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.
Project description:Background. Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. Methods. 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and leucocyte type heterogeneity. Findings. We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. Interpretation. Control of HIV viraemia after 96 weeks of ART initiation restores most of the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection.