RNA-seq of HIV-1 infected long-term non-progressors(LTNPs) and typical progressors(TPs)
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ABSTRACT:
PROVIDER: PRJEB42404 | ENA |
REPOSITORIES: ENA
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Project description:HIV-infected long-term non-progressors (LTNPs) are a special group of people who can naturally control HIV and maintain good host immunity. Their mechanism is related to viruses, host genetic characteristics, immune response and other factors, but the relationship between the activation level of innate immunity and long-term non-progression is not clear. Therefore,we hypothesize that LTNPs may have some founction to control the HIV replication in vivo.In this study, we used RNA-seq to investigate the transcription（lncRNA, miRNA and mRNA) profiles of LTNPs and typical progressors (TPs).This study is showing expression spectrum of mRNA and non-coding RNA between HIV-infected long-term non-progressors and typical progressors, and analyze the role of mRNA,IncRNA and miRNA in the HIV infected long-term non-progression based on whole transcriptome level.This study reveals the mechanism of different disease progression between LTNPs and TPs through functional enrichment analysis and differentially expressed genes(DEGs) analysis.
2021-02-10 | E-MTAB-9997 | biostudies-arrayexpress
Project description:HIV-infected slow-progressors (SP) represent a heterogeneous group of subjects who spontaneously control HIV infection without treatment for several years while showing moderate signs of disease progression. Here we determined the frequency of SP subjects who showed loss of HIV control within our Canadian Cohort of HIV+ Slow-Progressors and identified the proinflammatory cytokine IL-32 as a robust biomarker for control failure. Total cellular RNA was extracted from PBMC from 5 donors at two time points ('V1' before and 'V2' after loss of control, and only Long Term Non Progressors (LTNP) were part of the case study), along with 2 control Leuka914 and Aging106032 samples.
2015-12-31 | E-GEOD-74790 | biostudies-arrayexpress
Project description:In our cohort study for HIV, we have classified patients in 3 different groups, primarily on the basis latency period- Long term non-progressors (LTNP), Long term non-progressors NON-controllers (LNC), and regular progressors. individuals in these groups differ phenotypically as well as have significantly different levels of CD4+T cell counts and viral loads. Goal of the study is to explore the underlying novel mechanisms behind the differences in different patient classes of HIV using Next-Generation sequencing.
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Project description:We extracted total RNA from CD4+ T cells from 3 patient groups: chronic HIV-1 patients (CHI), long term non-progressors (LTNPs) and healthy controls (HC). Array results show that a large number of miRNAs are altered in HIV-1 infected patients compared to HC. Most of the differentially expressed miRNAs are down-regulated but there are some up-regulated miRNAs. A particular family of miRNAs which appear to be downregulated in HIV-1 infected patients is the let-7 family of miRNAs.
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Project description:HIV-infected slow-progressors (SP) represent a heterogeneous group of subjects who spontaneously control HIV infection without treatment for several years while showing moderate signs of disease progression. Here we determined the frequency of SP subjects who showed loss of HIV control within our Canadian Cohort of HIV+ Slow-Progressors and identified the proinflammatory cytokine IL-32 as a robust biomarker for control failure.
2015-12-31 | GSE74790 | GEO
Project description:We assessed correlates of protection from disease progression in a rare subset of HIV-infected individuals, viremic non-progressors (VNPs). These individuals have high viral load for several years, but in contrast to the majority of infected individuals, they do not progress to AIDS. Here we found this lack of progression was associated with selective preservation of two essential subsets of memory CD4+ T cells, central memory (TCM) and stem-cell memory (TSCM) cells. Compared to HIV-infected putative progressors, VNPs had higher proliferation of these indispensable subsets of memory cells, which was associated with the number of TCM. In addition, the long-lived CD4+ TCM and TSCM cells in VNPs had decreased HIV infection compared to the less critical effector memory CD4+ T cells, which indicates a possible mechanism by which VNPs maintain their CD4+ T cell pool after several years of infection, and remain free from AIDS progression. 6 HIV-infected patients fitting the clinical criteria of Viremic Non-Progressors were identified. VNPs were defined as having confirmed HIV-1 infection for at least 9 years with sustained plasma HIV RNA levels >10,000 copies/ml and maintenance of peripheral blood CD4+ T cell counts >500 cells/mm3 and a CD4% (of all lymphocytes) >15%. As controls, 7 HIV-infected Putative Progressors were identified. PPs were defined as having plasma HIV RNA levels >10,000 copies/mL, CD4+ T cell counts >400 cells/mm3 and having been initially infected with HIV 2-24 months prior to the index visit. The estimated date of initial HIV infection was calculated according to published algorithms that incorporate âde-tunedâ anti-HIV-1 antibody ELISA results or by a documented sero-conversion window of <6 months. All participants were required to be antiretroviral therapy (ART)-naïve. RNA from 6 VNP and 7 PPs was purified from PAXgene whole blood tubes and hybridized to Affymetrix U133 Plus 2.0 arrays. During data analysis, one VNP patient (PID 4015) was determined to be an outlier and removed from further analysis. Thus, 5 VNPs and 7 PPs are represented in this Series.
2016-05-15 | E-GEOD-57730 | biostudies-arrayexpress
Project description:We extracted total RNA from CD4+ T cells from 3 patient groups: chronic HIV-1 patients (CHI), long term non-progressors (LTNPs) and healthy controls (HC). Array results show that a large number of miRNAs are altered in HIV-1 infected patients compared to HC. Most of the differentially expressed miRNAs are down-regulated but there are some up-regulated miRNAs. A particular family of miRNAs which appear to be downregulated in HIV-1 infected patients is the let-7 family of miRNAs. In this study, we have included 8 healthy controls, 7 LTNPs and 7 CHI patients. We extracted RNA from magnetically separated CD4+ T cells (separated from peripheral blood mononuclear cells) and ran them on an Agilent miRNA array.
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Project description:We assessed correlates of protection from disease progression in a rare subset of HIV-infected individuals, viremic non-progressors (VNPs). These individuals have high viral load for several years, but in contrast to the majority of infected individuals, they do not progress to AIDS. Here we found this lack of progression was associated with selective preservation of two essential subsets of memory CD4+ T cells, central memory (TCM) and stem-cell memory (TSCM) cells. Compared to HIV-infected putative progressors, VNPs had higher proliferation of these indispensable subsets of memory cells, which was associated with the number of TCM. In addition, the long-lived CD4+ TCM and TSCM cells in VNPs had decreased HIV infection compared to the less critical effector memory CD4+ T cells, which indicates a possible mechanism by which VNPs maintain their CD4+ T cell pool after several years of infection, and remain free from AIDS progression.
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Project description:Immune activation in people living with HIV on anti-retroviral therapy is associated with increased risk of morbidity and mortality, but the underlying mechanisms are poorly understood. To identify whether perturbation of immunological pathways persist at systems level, we compared genome-wide whole blood transcriptomes from 26 people living with HIV on long-term anti-retroviral therapy with 12 HIV-negative healthy controls. All participants were Caucasian male adults recruited from London, UK. People living with HIV were on anti-retroviral therapy for a median of 8.5 years (interquartile range 3-16 years). They had undetectable plasma HIV viral load (<40 copies/ml) and median circulating CD4 counts of 703 cells/µl (interquartile range 491-841 cells/µl).
2021-02-26 | E-MTAB-8891 | biostudies-arrayexpress
Project description:Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy in primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of therapy in chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed exclusively during the initial 3-4 years of treatment; however, in patients who started antiretroviral therapy in acute infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. Moreover, gene transcripts in CD4 T cells associated with the total viral CD4 T cell reservoir size frequently correlated with the relative proportion of these long-lived CD4 T cell subsets, suggesting shared gene expression signatures for maintaining HIV-1 persistence and preservation of long-lasting CD4 T cell subsets. Despite effective suppression of viral antigens for >10 years, HIV-1-specific T cell responses remained continuously detectable in both study groups. Together, these data suggest that although early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients attractive candidates for future interventional studies aiming at HIV-1 eradication and cure.
2017-01-01 | GSE53527 | GEO