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Comparative Expression Profile of miRNA and mRNA in Primary Peripheral Blood Mononuclear Cells Infected with Human Immunodeficiency Virus (HIV-1) [mRNA]

ABSTRACT: Host cells respond to exogenous infectious agents such as viruses, including HIV-1. Studies have evaluated the changes associated with virus infection at the transcriptional and translational levels of the cellular genes involved in specific pathways. While this approach is useful, in our view it provides only a partial view of genome-wide changes. Recently, technological advances in the expression profiling at the microRNA (miRNA) and mRNA levels have made it possible to evaluate the changes in the components of multiple pathways. To understand the role of miRNA and its interplay with host cellular gene expression (mRNA) during HIV-1 infection, we performed a comparative global miRNA and mRNA microarray using human PBMCs infected with HIV-1. The PBMCs were derived from multiple donors and were infected with virus generated from the molecular clone pNL4-3. The results showed that HIV-1 infection led to altered regulation of 21 miRNAs and 444 mRNA more than 2-fold, with a statistical significance of p<0.05. Furthermore, the differentially regulated miRNA and mRNA were shown to be associated with host cellular pathways involved in cell cycle/proliferation, apoptosis, T-cell signaling, and immune activation. We also observed a number of inverse correlations of miRNA and mRNA expression in infected PBMCs, further confirming the interrelationship between miRNA and mRNA regulation during HIV-1 infection. These results for the first time provide evidence that the miRNA profile could be an early indicator of host cellular dysfunction induced by HIV-1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33877 | GEO | 2011/11/23

SECONDARY ACCESSION(S): PRJNA154221

REPOSITORIES: GEO

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Comparative Expression Profile of miRNA and mRNA in Primary Peripheral Blood Mononuclear Cells Infected with Human Immunodeficiency Virus (HIV-1) [miRNA]

Project description:Host cells respond to exogenous infectious agents such as viruses, including HIV-1. Studies have evaluated the changes associated with virus infection at the transcriptional and translational levels of the cellular genes involved in specific pathways. While this approach is useful, in our view it provides only a partial view of genome-wide changes. Recently, technological advances in the expression profiling at the microRNA (miRNA) and mRNA levels have made it possible to evaluate the changes in the components of multiple pathways. To understand the role of miRNA and its interplay with host cellular gene expression (mRNA) during HIV-1 infection, we performed a comparative global miRNA and mRNA microarray using human PBMCs infected with HIV-1. The PBMCs were derived from multiple donors and were infected with virus generated from the molecular clone pNL4-3. The results showed that HIV-1 infection led to altered regulation of 21 miRNAs and 444 mRNA more than 2-fold, with a statistical significance of p<0.05. Furthermore, the differentially regulated miRNA and mRNA were shown to be associated with host cellular pathways involved in cell cycle/proliferation, apoptosis, T-cell signaling, and immune activation. We also observed a number of inverse correlations of miRNA and mRNA expression in infected PBMCs, further confirming the interrelationship between miRNA and mRNA regulation during HIV-1 infection. These results for the first time provide evidence that the miRNA profile could be an early indicator of host cellular dysfunction induced by HIV-1. Total RNA isolated from PBMC subjected to 7 days of HIV-1 infection compared to uninfected control PBMC

2011-11-23 | E-GEOD-33837 | biostudies-arrayexpress

Comparative Expression Profile of miRNA and mRNA in Primary Peripheral Blood Mononuclear Cells Infected with Human Immunodeficiency Virus (HIV-1) [mRNA]

2011-11-23 | E-GEOD-33877 | biostudies-arrayexpress

Comparative Expression Profile of miRNA and mRNA in Primary Peripheral Blood Mononuclear Cells Infected with Human Immunodeficiency Virus (HIV-1) [miRNA]

2011-11-23 | GSE33837 | GEO

miRNA expression profiles in productively HIV-1 infected and bystander primary human CD4+ T-cells

Project description:CD4+ T-cells are the main target of HIV-1 and several host factors can positively or negatively modulate HIV-1 infection of these cells. MiRNAs aresmall regulatory RNAs that are involved in the regulation of basic cellular functions. They are also increasingly recognized as host factors regulatingHIV-1 infection, replication and persistence. In order to identify miRNAs involved in HIV-1 infection of CD4+ T-cells, we performed globaltranscriptomic analyses of productively infected and HIV-1 exposed but non infected bystander CD4+ T-cells and compared their MIRNA profiles with uninfected cells. Theseanalyses were performed in CD4+T-cells isolated from 3 different healthy blood donors. Both miRNA and mRNA expression profiles were compared. Our results show that bystander and uninfected CD4+ T-cells do not display important differences in their miRNA expression profiles even though their respectivemRNA expression profiles were markedly different. In contrast, both mRNA and miRNA expressionprofiles from productively infected CD4+ T-cells were significantly different from those of uninfected cells. Overall, these results suggest that HIV-1infection impacts the miRNA expression profile of primary CD4+ T-cells.

2024-08-02 | GSE247194 | GEO

mRNA expression profiles in productively HIV-1 infected and bystander primary human CD4+ T-cells

2024-08-02 | GSE247191 | GEO

Comparison of transcriptional profiles of PBMCs from HIV-infected rapid progressors and chronic progressors

Project description:A significant percentage of HIV-infected individuals experience a sharp decline in CD4+ T cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) versus chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. mRNA and miRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111Â±22 days (MeanÂ±SD) of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by receiver operating characteristic analysis and Kaplan-Meier survival analysis. Pathway enrichment analysis showed that genes with deregulated expression in RPs are primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a and -503) in RPs were significantly decreased compared to those in CPs (P<0.05). The decreased expression of these miRNAs was associated with rapid disease progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection. A cohort of primary HIV infected individuals with different disease outcome were enrolled in this study. We included 6 individuals with rapid disease progression (RP), seven with chronic disease progression (CP). The HIV infected individuals were never on therapy before the time of sample taken.

2013-05-01 | E-GEOD-44216 | biostudies-arrayexpress

In depth analysis of the interaction of HIV 1 with cellular microRNA biogenesis and effector mechanisms

Project description:The question of how HIV 1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4+ PBMCs and macrophages) to unequivocally demonstrate that HIV 1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection of T cells by HIV 1 has only a modest effect on the expression of cellular miRNAs at early times after infection. Comprehensive analysis of miRNA binding to the HIV 1 genome using the photoactivatable ribonucleoside-induced crosslinking and immunoprecipitation (PAR-CLIP) technique revealed several binding sites for cellular miRNAs, a subset of which were shown to be capable of mediating miRNA-mediated repression of gene expression. However, the main finding from this analysis is that HIV 1 transcripts are largely refractory to miRNA binding, most probably due to extensive viral RNA secondary structure. Together, these data demonstrate that HIV 1 neither encodes viral miRNAs nor strongly influences cellular miRNA expression, at least early after infection, and imply that HIV 1 transcripts have evolved to avoid inhibition by pre-existing cellular miRNAs by adopting extensive RNA secondary structures that occlude most potential miRNA binding sites. Small RNA profiling of HIV-1 infected cells through total small RNA deep sequencing and identification of RNA-induced silencing complex (RISC)-associated HIV-1 sequences through the RNP-immunoprecipitation technique of PAR-CLIP on RISC

2014-07-31 | E-GEOD-59944 | biostudies-arrayexpress

In depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms

Project description:The question of how HIV-1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4+ PBMCs and macrophages) to unequivocally demonstrate that HIV-1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection of T cells by HIV-1 has only a modest effect on the expression of cellular miRNAs at early times after infection. Comprehensive analysis of miRNA binding to the HIV-1 genome using the photoactivatable ribonucleoside-induced crosslinking and immunoprecipitation (PAR-CLIP) technique revealed several binding sites for cellular miRNAs, a subset of which were shown to be capable of mediating miRNA-mediated repression of gene expression. However, the main finding from this analysis is that HIV-1 transcripts are largely refractory to miRNA binding, most probably due to extensive viral RNA secondary structure. Together, these data demonstrate that HIV-1 neither encodes viral miRNAs nor strongly influences cellular miRNA expression, at least early after infection, and imply that HIV-1 transcripts have evolved to avoid inhibition by pre-existing cellular miRNAs by adopting extensive RNA secondary structures that occlude most potential miRNA binding sites.

2014-07-31 | GSE59944 | GEO

Transcriptomic profiling of micro RNAs in mock-infected cells and an in vitro model of HIV latency before and after activation

Project description:Purpose: The goal of this study is to identify host micro RNAs (miRNAs) whose expression is dysregulated during HIV latency, cell activation and productive infection. This information provides a mechanistic insight into an additional layer of miRNA-mediated regulation of gene expression and cellular pathways that are involved in HIV latency establishment and maintenance. Methods: An in vitro model of HIV latency and mock-infected cells before and after activation with antiCD3/antiCD28 coated magnetic beads was used for miRNA expression profiling using small RNA sequencing (smRNA-Seq). Results: Read counts of the 418 miRNAs survived filtering. Differential expression analysis identified 26 miRNAs dysregulated in latency. Messenger RNA (mRNA) targets and cellular pathways enriched for mRNA targets were identified using several analytical methods. Our analyses showed that many protein-coding genes and pathways targeted by dysregulated miRNAs have relevance to regulation of HIV expression or establishment of HIV latency. The p53 signalling pathway was found among pathways that were targeted by dysregulated miRNAs at a greater level than expected by chance. Conclusions: The present study identifies miRNAs dysregulated during HIV latency and provides a mechanistic insight into regulation of the p53 pathway via miRNAs that may contribute to latency establishment.

2020-11-02 | GSE153094 | GEO

Comparison of transcriptional profiles of PBMCs from HIV-infected rapid progressors and chronic progressors

Project description:A significant percentage of HIV-infected individuals experience a sharp decline in CD4+ T cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) versus chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. mRNA and miRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111±22 days (Mean±SD) of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by receiver operating characteristic analysis and Kaplan-Meier survival analysis. Pathway enrichment analysis showed that genes with deregulated expression in RPs are primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a and -503) in RPs were significantly decreased compared to those in CPs (P<0.05). The decreased expression of these miRNAs was associated with rapid disease progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection.

2013-05-01 | GSE44216 | GEO

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