Next Generation Sequencing Facilitates Quantitative Analysis of HIV Elite controller, HIV ART, HIV ART-naive and healthy control Transcriptomes
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PROVIDER: PRJNA660430 | ENA |
REPOSITORIES: ENA
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Project description:A small group of HIV-1-infected individuals, termed elite controllers (ECs), display control of HIV replication in the absence of antiretroviral therapy (ART). However, the mechanisms of resistance to HIV in ECs remains largely unknown. To identify host factors specific to the ECs that might be involved in controlling HIV infection, we performed RNA-seq transcriptome analysis, and a total of 44 samples were included. The monocytes from each sample were enriched, sequenced, and subjected to comparative transcriptome analysis to screen candidate genes that might affect resistance to HIV infection. we found several candidate genes with highly divergent expression that might contribute to the different outcomes of HIV infection in ECs and non-ECs. This finding will help elucidate the mechanisms by which ECs restrict HIV replication and represents a new approach for treatment of HIV.
2021-12-09 | GSE157198 | GEO
Project description:The virus-specific CD4+ T cell dysfunction associated with failure to control chronic infections is poorly understood in humans. An issue of critical clinical relevance is the lack of restoration of effective anti-HIV immunity after suppressive ART: viral rebound is the rule after cessation of therapy. Whether persistent HIV-specific CD4+ T cell dysfunction on ART contribute to this failed response is an important, yet unresolved, question. To decipher the consequences of ongoing viral antigen exposure, versus the results of durable cell-fate decision programs that would persist in former CP individuals after successful viral suppression on ART, we compared trancriptional profiles of chronic progressor before and after the initiation of ART, with the transcriptional profiles of elite controllers, HIV-infected individuals that spontaneously control viral load. Suppression of viremia by ART resulted in a distinct transcriptional landscape, with reduction in TFH gene expression but no correction of the TH1, TH17 and TH22 gene levels compared to the elite controller profile.
2019-07-15 | GSE128296 | GEO
Project description:Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers. Results: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200cp/ml) and 5 uninfected individuals (HIV-) through TaqMan® Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs overcame significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. Conclusions: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia. Peripheral blood mononuclear cell samples were from five uninfected controls, eight viremic HIV-1-infected patients, eight HIV-1 elite controllers with undetectable viral load and eight HIV-1antiretroviral treated individuals with undetectable viral load.
2014-05-06 | E-GEOD-57323 | biostudies-arrayexpress
Project description:A paired analysis of peripheral blood mononuclear cells (PBMCs) isolated before and after antiretroviral therapy (ART) from a robust number of HIV-infected patients (N=36). Results identify a total of 4,157 DEGs following ART in HIV-infected participants and the transition from a period of active virus replication before ART to one of viral suppression This study evaluated PBMC gene expression in cells from 36 (4 dropped from analysis) recently HIV-infected individuals to identify differentially expressed genes following 48 weeks of ART
2013-09-10 | E-GEOD-44228 | biostudies-arrayexpress
Project description:Th17 cells are rapidly depleted during HIV infection and their frequencies and functions are not fully restored by antiretroviral therapy (ART). In addition, Th17 cells contribute to viral persistence during ART. However, molecular mechanisms underlying these observations remain understudied. MemCCR6+ cells from STs vs. HDs showed alterations in the NOTCH and TGF-β1/smad2-3 pathways, indicative of impairments in their differentiation and stability. Consistently, the RORγt/C2 repressor NR1D1 was upregulated, while Semaphorin 4D, a RORγt/C2 inducer, was decreased in MemCCR6+ cells from STs vs. HDs. Frequencies of Th17 and Th1/Th17 cells within total MemCCR6+ cells were lower in STs and ECs compared to HD individuals, and expressed higher levels of activation and senescence/exhaustion markers. As a result, MemCCR6+ cells from STs produced less IL-17A/F, IL-22, and IFN-γ in vitro compared to HDs. Downregulation of HIV restriction factors (SERINC3, KLF3, and RNF125) and HIV inhibitors (tetraspanins), along with increased expression of MRE11 in MemCCR6+ cells from ST individuals supported higher susceptibility/permissiveness to HIV infection. MemCCR6+ cells from STs and ECs had lower TFAP4 expression and increased expression of EED and TP53BP1 vs. HDs, which is associated to HIV persistence. Markers of DNA damage/modification were elevated in STs and ECs compared to HDs, including NASP, RPA2, H2AX, PARP, and DNA methylases DNMT1/DNMT3A. Similar to the ST group, MemCCR6+ cells in ECs showed decreased expression of Semaphorin 4D and Notch1, along with higher expression of NR1D1 compared to HD donors. Despite successful ART, the transcriptional signature of MemCCR6+ cells revealed impaired differentiation, stability, functions, DNA damage/modifications, and higher susceptibility to HIV infection and viral persistence.
2024-06-30 | GSE252771 | GEO
Project description:Elite controllers maintain HIV-1 viral loads below the limit of detection. The mechanisms responsible for this phenomenon are poorly understood. As microRNAs (miRNAs) are regulators of gene expression and some of them modulate HIV infection, we have studied the miRNA profile in plasma from HIV elite controllers and chronically infected individuals and compared against healthy donors. Several miRNAs correlate with CD4+ T cell count or with the known time of infection. No significant differences were observed between elite controllers and healthy donors; however, 16 miRNAs were different in the plasma of chronic infected versus healthy donors. In addition, levels of hsa-miR-29b-3p, hsa-miR-33a-5p and hsa-miR-146a-5p were higher in plasma from elite controllers than chronic infected and hsa-miR-29b-3p and hsa-miR-33a-5p overexpression significantly reduced the viral production in MT2 cells. Therefore, levels of circulating miRNAs might be of diagnostic and/or prognostic value for HIV infection. Additionally, hsa-miR-29b-3p and miR-33a-5p may be used in therapeutic strategies. An exploratory cross-sectional study of microRNA levels in EDTA plasma samples. Plasma samples were obtained from 24 subjects and were classified in 3 groups, 9 Elite Controllers (defined as individuals with plasma viral load (PVL) < 50 copies/ml, CD4 count >350/ml), 9 chronic HIV patients (CH) under anti-retroviral treatment and 6 healthy HIV negative donors (HD). This study was approved by the HuM-CM-)sped Foundation Ethics Committee and informed consent was obtained from all subjects.
2014-08-04 | E-GEOD-58868 | biostudies-arrayexpress
Project description:Elite controllers maintain HIV-1 viral loads below the limit of detection. The mechanisms responsible for this phenomenon are poorly understood. As microRNAs (miRNAs) are regulators of gene expression and some of them modulate HIV infection, we have studied the miRNA profile in plasma from HIV elite controllers and chronically infected individuals and compared against healthy donors. Several miRNAs correlate with CD4+ T cell count or with the known time of infection. No significant differences were observed between elite controllers and healthy donors; however, 16 miRNAs were different in the plasma of chronic infected versus healthy donors. In addition, levels of hsa-miR-29b-3p, hsa-miR-33a-5p and hsa-miR-146a-5p were higher in plasma from elite controllers than chronic infected and hsa-miR-29b-3p and hsa-miR-33a-5p overexpression significantly reduced the viral production in MT2 cells. Therefore, levels of circulating miRNAs might be of diagnostic and/or prognostic value for HIV infection. Additionally, hsa-miR-29b-3p and miR-33a-5p may be used in therapeutic strategies.
2014-08-04 | GSE58868 | GEO
Project description:Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers Results: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200cp/ml) and 5 uninfected individuals (HIV-) through TaqMan® Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs overcame significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. Conclusions: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.
2014-05-06 | GSE57323 | GEO
Project description:Genome wide DNA methylation profiling of CD4 T cells from uninfected and HIV-infected individuals (viremic, ART-suppressed and elite controllers [EC]) The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 485,577 CpGs in DNA from peripheral CD4 T cells samples. Samples included: 22 from HIV-uninfected individuals (uninfected group), 42 from HIV-infected individuals (21 from HIV-infected viremic (viremic group) and 21 from the same participants after viral suppression (viral load< 50 copies HIV-1 RNA/plasma) by antiretroviral therapy administrarion (ART group), and 21 from elite controllers (EC group)
2023-01-16 | GSE143942 | GEO
Project description:Goal of this study was to assess the levels of protection and investigate cellular, humoral, and mucosal immune correlates on the functional and gene transcriptional levels in elite-controller macaques following high dose SIV challenge.
2010-08-24 | GSE23722 | GEO