Transcriptomic study reveals changes of lncRNAs in PBMCs from HIV-1 patients before and after ART
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ABSTRACT:
PROVIDER: PRJNA984233 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24947564_1.fastq.gz | Fastqsanger.gz | |||
| SRR24947564_2.fastq.gz | Fastqsanger.gz | |||
| SRR24947565_1.fastq.gz | Fastqsanger.gz | |||
| SRR24947565_2.fastq.gz | Fastqsanger.gz | |||
| SRR24947566_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Many studies have shown that long noncoding RNAs (lncRNAs) derived from the host and human immunodeficiency virus (HIV) itself play important roles in virus-host interactions and viral pathogenesis. It is unclear whether lncRNAs were involved in ART therapy of HIV/AIDS patients. Methods: Six HIV/acquired immunodeficiency syndrome (AIDS) subjects pre-HAART and post-HAART with effective control of plasma viremia (<20 HIV RNA copies/ml) and 6 healthy subjects were recruited in this study to perform RNA sequencing. The expression profiles of lncRNAs and mRNAs were obtained, to exploration of the potential roles of lncRNAs, trans- and cis-acting analysis was used. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to sort out functional categories of genes. Results: We identified a total of 974 lncRNAs whose expression levels were restored to normal after ART therapy. The results of the cis-acting analysis showed that only six lncRNAs have cis-regulated target genes, among which the target gene RP11-290F5.1, interferon regulatory factors 2 (IRF2), could promote HIV replication. We also identified lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression between pre- and post-HAART, and the differences were significant. We selected lncRNA CTB-119C2.1 for qRT–PCR verification, and the results were consistent with those of RNA-seq. RAB3A and GADD45A, two of the lncRNA CTB-119C2.1-associated genes, have been shown to be associated with HIV infection. KEGG analysis of lncRNA CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway or pathways related to cell circulation and DNA replication. Conclusion: In this study, we used RNA-seq to systematically compare the expression profiles of lncRNAs in HIV subjects between untreated and treated time points. We successfully identified some lncRNAs with differential expression during certain periods (no HIV infection, HIV infection before treatment, and after treatment). Their expression is associated with HIV viral loads, and some of their regulating genes were found to be involved in HIV pathogenesis through bioinformatic analysis. These findings could help to reveal the underlying molecular mechanism of the progression of HIV infection.
2023-12-25 | GSE235038 | GEO
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: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
2013-09-10 | GSE44228 | GEO
Project description:To understand how HIV and timing of ART initiation affect the transcriptional profile of Mtb-specific CD4 T cells, we performed 10X single-cell RNA sequencing comparing Mtb-specific CD4 T cell transcriptomes from people without HIV, people with HIV prior to ART, and people with HIV after ART from the Mombasa Cohort in Mombasa, Kenya. PBMCs were stimulated overnight with Mycobacterium tuberculosis whole cell lysate and CD40L+CD69+ Mtb-specifc CD4 T cells were sorted for sequencing.
2025-07-10 | GSE299662 | GEO
Project description:Blood from ART-suppressed people with HIV (PWH) were characterized by bulk RNAseq analysis of total PBMCs, or of purified CD4+ T cells from PBMCs. Specimens were obtained from four cohorts: CLEAR, TEACH, REDUC, and ACTG A5345. All participants enrolled in these cohorts underwent analytical treatment interruption (ATI) and were monitored for time-to-rebound of HIV viremia.
2026-04-17 | GSE290636 | GEO
Project description:Introduction: HIV infection causes pathologic changes in the natural killer (NK) cell compartment that can be only partially restored by antiretroviral therapy (ART). We investigated NK cells phenotype and function in children with perinatally acquired HIV (PHIV) and long term viral control (5years) due to effective ART in a multicentre cross-sectional study (CARMA, EPIICAL consortium). The impact of age at ART start and viral reservoir was also evaluated. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from 40 PHIV that started ART within two years of life (early treated patients, ET ≤ 6 months; late treated patients, LT > 6 months), with at least five years of HIV-1 suppression (< 40 HIV copies/ml), were collected between November 2017 and August 2018. NK phenotype and function were analysed by flow cytometry and transcriptional profile of PBMCs by RNA-Seq. HIV-1 DNA was measured by real-time PCR. Data were analysed by Spearman correlation plots and multivariable Poisson regression model (adjusted for baseline %CD4 and RNA HIV viral load and for age at ART start as interaction term, either ET or LT) to explore the association between NK cell parameters and HIV reservoir modulated by age at ART start. Results: A significantly higher frequency of CD56neg NK cells was found in LT compared with ET. We further found in LT a positive correlation of CD56neg NK with HIV-1 DNA. LT also displayed increased expression of the NKG2D and NKp46 activating receptors and perforin compared with ET. Moreover, CD107a+ and IFN-γ+ frequencies in non-stimulated NK were associated with HIV-1 DNA in LT patients. Finally, RNA-Seq analysis showed in LT an upregulation of genes related to NK activating pathways and susceptibility to apoptosis compared with ET. Conclusions: We show that ET present a preserved NK compartment compared with LT, which is associated with lower HIV-1 reservoir and persist despite long-term viral control due to effective ART.
2021-07-14 | GSE168658 | 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:HIV reservoirs persist despite successful antiretroviral therapy (ART) and are a major obstacle to the eradication and cure of HIV. The mature monocyte subset, CD14+CD16+, contributes to viral reservoirs and HIV-associated comorbidities. Only a subset of monocytes harbors HIV (HIV+), while the rest remain uninfected, exposed cells (HIVexp). We developed an innovative single cell RNA sequencing (scRNAseq) pipeline that detects HIV and host transcripts simultaneously, enabling us to examine differences between HIV+ and HIVexp mature monocytes. Using this, we characterized uninfected, HIV+, and HIVexp primary human mature monocytes with and without ART. We showed that HIV+ mature monocytes do not form their own cluster separately from HIVexp but can be distinguished by significant differential gene expression. We found that ART decreased levels of unspliced HIV transcripts potentially by modulating host transcriptional regulators shown to decrease viral infection and replication. We also identified and characterized mature monocyte subpopulations differentially impacted by HIV and ART. We identified genes dysregulated by ART in HIVexp monocytes compared to their uninfected counterpart and, of interest, the junctional protein ALCAM, suggesting that ART impacts monocyte functions. Our data provide a novel method for simultaneous detection of HIV and host transcripts. We identify potential targets, such as those genes whose expression is increased in HIV+ mature monocytes compared to HIVexp, to block their entry into tissues, preventing establishment/replenishment of HIV reservoirs even with ART, thereby reducing and/or eliminating viral burden and HIV-associated comorbidities. Our data also highlight the heterogeneity of mature monocyte subsets and their potential contributions to HIV pathogenesis in the ART era.
2020-07-08 | GSE153958 | GEO
Project description: Not available
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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