HIV-1 Tat protein exposure alters the morphological characteristics and gene expression in the primary mouse cortex endothelial cells and human brain microvascular endothelial cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE307483 | GEO | 2025/12/15
REPOSITORIES: GEO
Similar Datasets
Project description:HIV-1-associated neurocognitive disorders (HAND) are highly prevalent in the era of combination of antiretroviral therapies. Recent studies suggest that damage of blood-brain barrier (BBB) may serve as an early biomarker of cognitive dysfunction in people living with HIV. In this study, we focused on endothelial cells, the core component of the BBB, to investigate the effects of HIV-1 transactivator of transcription (Tat) protein on their morphological alterations and gene expression profiles of human brain microvascular endothelial cells (HBMVECs). Our results demonstrated that Tat-exposed HBMVECs showed reduced CD31 expression, increased phalloidin staining intensity, and activation of inflammatory response pathways as revealed by RNA-seq analysis.
2026-01-21 | GSE307481 | GEO
Project description:Anti-retroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection from a fatal illness to a chronic condition by controlling viral replication and restoring immune function. However, chronic T-cell activation can be observed in 20-35% of individuals on ART, resulting in an immune reconstitution inflammatory syndrome (IRIS) [1-3]. IRIS involving the CNS can result in permanent disability and death [4]. Tat is a viral protein produced in HIV-infected cells and released into the extracellular space [5]. We show that the secreted-Tat protein activated uninfected T-cells in an antigen-independent manner without inducing proliferation. Notably, Tat induced the secretion of IL-17 from T-cells and increased the percentage of T-cells with a Th17 phenotype. T-cell activation was independent of the T-cell receptor but dependent on endocytosis of Tat and activation of vascular endothelial growth factor receptor 2 (VEGFR2). Tat induced global changes in histone acetylation and increased HIV infection in non-replicating T-cells. Furthermore, in an individual with CNS IRIS, Tat expressing infiltrates and secretion of IL-17 was detected in the absence of viral replication in the brain. Thus Tat can induce T-cell activation in a paracrine and autocrine manner resulting in propagation of inflammation and increased virulence. 12 Human samples in 6 pairs: 6 Human T cell HIV tat exposed 0hrs, 6 Human T cell HIV tat exposed 24hrs
2013-08-02 | E-GEOD-44460 | biostudies-arrayexpress
Project description:Anti-retroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection from a fatal illness to a chronic condition by controlling viral replication and restoring immune function. However, chronic T-cell activation can be observed in 20-35% of individuals on ART, resulting in an immune reconstitution inflammatory syndrome (IRIS) [1-3]. IRIS involving the CNS can result in permanent disability and death [4]. Tat is a viral protein produced in HIV-infected cells and released into the extracellular space [5]. We show that the secreted-Tat protein activated uninfected T-cells in an antigen-independent manner without inducing proliferation. Notably, Tat induced the secretion of IL-17 from T-cells and increased the percentage of T-cells with a Th17 phenotype. T-cell activation was independent of the T-cell receptor but dependent on endocytosis of Tat and activation of vascular endothelial growth factor receptor 2 (VEGFR2). Tat induced global changes in histone acetylation and increased HIV infection in non-replicating T-cells. Furthermore, in an individual with CNS IRIS, Tat expressing infiltrates and secretion of IL-17 was detected in the absence of viral replication in the brain. Thus Tat can induce T-cell activation in a paracrine and autocrine manner resulting in propagation of inflammation and increased virulence.
2013-08-02 | GSE44460 | GEO
Project description:HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFN’s. The three alleles and mutants, with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFN’s. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. To investigate what domain of Tat are critical to the host-pathogen interactions that are Tat-dependent during HIV infection, we evaluated a variety of Tat-mutants and found that in antigen presenting cells, blood-derived myeloid iDC and macrophages, the second exon of Tat reduces innate immunological responses which are maximal when a Single exon Tat is expressed.
2013-06-01 | GSE42925 | GEO
Project description:HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFNM-bM-^@M-^Ys. The three alleles and mutants, with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFNM-bM-^@M-^Ys. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. To investigate what domain of Tat are critical to the host-pathogen interactions that are Tat-dependent during HIV infection, we evaluated a variety of Tat-mutants and found that in antigen presenting cells, blood-derived myeloid iDC and macrophages, the second exon of Tat reduces innate immunological responses which are maximal when a Single exon Tat is expressed. 1X10e6 macrophages were infected with HIVBal (20 ng of p24/ 106 cells) for 10 days and with adenoviruses expressing TatHXB2 or LacZ control (5 pfu per cell). Cells infected with Ad-Tat or Ad-LacZ were collected at 24 hours and cells infected with HIV or treated with medium were harvested at 7d and 10d post-infection. THP-Mac were infected with Ad-Tat or Ad-tTA control for 24 hours. RNA was isolated and mRNA expression levels were analyzed by microarrays. adenovirus expressing HIV Tat for 30 hours. and then RNA was isolated, labeled, and prepared for hybridization on Affymetrix microarrays.
2013-06-01 | E-GEOD-42925 | biostudies-arrayexpress
Project description:HIV-1 Tat protein exposure alters the morphological characteristics and gene expression in the primary mouse cortex endothelial cells and human brain microvascular endothelial cells
| PRJNA1321806 | ENA
Project description:Our previous work demonstrated that HIV-1 infection progressively reduces TCR/CD3 expression due to a defect in CD3g gene transcripts. We further found that knocking down expression of the viral tat and/or nef genes was correlated with CD3g transcript and TCR/CD3 surface receptor levels on HIV-1 infected cells. This study was undertaken to investigate the direct effect of HIV-1 Tat expression on the TCR/CD3 machinery. Progressive downregulation from TCR/CD3hi to TCR/CD3lo to TCR/CD3− was observed on Tat expressing cells in a manner that emulated HIV-1 infection, with a lack of CD3g transcripts again responsible for the defect. When Tat cell cultures containing a mixture of TCR/CD3 surface densities were separated into TCR/CD3hi and TCR/CD3lo/− populations, they quickly reverted to a mixed CD3 phenotype. Thus, the progression TCR/CD3hi to TCR/CD3lo to TCR/CD3− is an active, reversible process with receptor levels fluctuating in response to intracellular dynamics. Examination of tat mutants found that the regions involved in Tat-mediated transactivation and TAR binding are required for TCR/CD3 downregulation while the lysine at position 28 and Tat exon 2 are dispensable. Global gene expression, assessed in association with TCR/CD3 downregulation in HIV-1 infected and Tat expressing cells, detected broad suppression of TCR/CD3 signaling, co-stimulation and negative regulatory genes along with target transcription factors, ligands and receptors. A significant subset of the genes altered in HIV-1 infected cells was specifically targeted by Tat in association with TCR/CD3 loss. Our finding that Tat negatively regulates many facets of the TCR/CD3 machinery has important implications for disease pathogenesis. We used microarrays to investigate changes in CD4+ T cell gene expression induced by expression of the HIV-1 Tat protein.
2015-12-31 | GSE33705 | GEO
Project description:Our previous work demonstrated that HIV-1 infection progressively reduces TCR/CD3 expression due to a defect in CD3g gene transcripts. We further found that knocking down expression of the viral tat and/or nef genes was correlated with CD3g transcript and TCR/CD3 surface receptor levels on HIV-1 infected cells. This study was undertaken to investigate the direct effect of HIV-1 Tat expression on the TCR/CD3 machinery. Progressive downregulation from TCR/CD3hi to TCR/CD3lo to TCR/CD3â was observed on Tat expressing cells in a manner that emulated HIV-1 infection, with a lack of CD3g transcripts again responsible for the defect. When Tat cell cultures containing a mixture of TCR/CD3 surface densities were separated into TCR/CD3hi and TCR/CD3lo/â populations, they quickly reverted to a mixed CD3 phenotype. Thus, the progression TCR/CD3hi to TCR/CD3lo to TCR/CD3â is an active, reversible process with receptor levels fluctuating in response to intracellular dynamics. Examination of tat mutants found that the regions involved in Tat-mediated transactivation and TAR binding are required for TCR/CD3 downregulation while the lysine at position 28 and Tat exon 2 are dispensable. Global gene expression, assessed in association with TCR/CD3 downregulation in HIV-1 infected and Tat expressing cells, detected broad suppression of TCR/CD3 signaling, co-stimulation and negative regulatory genes along with target transcription factors, ligands and receptors. A significant subset of the genes altered in HIV-1 infected cells was specifically targeted by Tat in association with TCR/CD3 loss. Our finding that Tat negatively regulates many facets of the TCR/CD3 machinery has important implications for disease pathogenesis. We used microarrays to investigate changes in CD4+ T cell gene expression induced by expression of the HIV-1 Tat protein. Examine changes in gene expression in HIV-1 Tat transduced cells compared with cells transduced with an antisense Tat sequence used as a control.
2015-12-31 | E-GEOD-33705 | biostudies-arrayexpress
Project description:HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFN’s. The three alleles and mutants, with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFN’s. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. We investigated the effect of various Tat alleles and mutants on host cell gene expression in immature dendritic cells (iDC). The cells were infected with adenoviruses expressing the Tat constructs.
2013-06-01 | GSE42924 | GEO
Project description:HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFNM-bM-^@M-^Ys. The three alleles and mutants, with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFNM-bM-^@M-^Ys. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. We investigated the effect of various Tat alleles and mutants on host cell gene expression in immature dendritic cells (iDC). The cells were infected with adenoviruses expressing the Tat constructs. The Tat alleles and mutants are under a tetracycline inducible promoter and are expressed only in cells co-infected with Ad-tTA, which expresses the tetracycline responsive transactivator. 10e6 iDC were infected with 5 plague forming units per cell of the adenoviruses and cells were collected 10 and 20 hours post-infection. RNA was isolated and mRNA expression levels were analyzed by microarrays. As controls we used cells that were left uninfected and cells that were infected with Ad-LacZ, which expresses beta-galactosidase.
2013-06-01 | E-GEOD-42924 | biostudies-arrayexpress