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Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [bulk RNA-seq]

ABSTRACT: Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [bulk RNA-seq]

PROVIDER: PRJNA601238 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10894924_1.fastq.gz	Fastqsanger.gz
	SRR10894924_2.fastq.gz	Fastqsanger.gz
	SRR10894925_1.fastq.gz	Fastqsanger.gz
	SRR10894925_2.fastq.gz	Fastqsanger.gz
	SRR10894926_1.fastq.gz	Fastqsanger.gz

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Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [scRNA-seq]

Project description:HIV-Associated Neurocognitive Disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a proper model. We developed a human-induced pluripotent stem cell (HiPSC) based model, independently differentiating HiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV-infection and ART. Single cell RNAseq analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound EFZ mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in TNFa production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.

2020-04-27 | GSE143686 | GEO

Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection

Project description:Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection

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Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [bulk RNA-seq]

2020-04-27 | GSE143685 | GEO

Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [scRNA-seq]

Project description:Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [scRNA-seq]

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Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy

Project description:Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy

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Neuroinflammation and EIF2 Signaling Persist despite Antiretroviral Treatment in an hiPSC Tri-culture Model of HIV Infection.

Project description:HIV-associated neurocognitive disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a representative model. We developed a human-induced pluripotent stem cell (hiPSC)-based model, independently differentiating hiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV infection and ART. Single-cell RNA sequencing analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound efavirenz (EFZ) mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in transforming growth factor α production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.

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Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-27 | GSE143687 | GEO

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

Project description:Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed microarray analysis using Affymetrix Arrays in portmortem brain tissues from seven treated and eight untreated HAND patients and six uninfected controls.

2011-09-24 | E-GEOD-28160 | biostudies-arrayexpress

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

2011-09-25 | GSE28160 | GEO

Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy

Project description:T cell dysfunction occurs early following HIV infection, impacting the emergence of non-AIDS morbidities and limiting curative efforts. ART initiated during primary HIV infection (PHI) can reverse this dysfunction, but the extent of recovery is unknown. We studied 66 HIV-infected individuals treated from early PHI with up to three years of ART. Compared with HIV-uninfected controls, CD4 and CD8 T cells from early HIV infection were characterised by T cell activation and increased expression of the immune checkpoint receptors (ICRs) PD1, Tim-3 and TIGIT. Three years of ART lead to partial – but not complete – normalisation of ICR expression, the dynamics of which varied for individual ICRs. For HIV-specific cells, epigenetic profiling of tetramer-sorted CD8 T cells revealed that epigenetic features of exhaustion typically seen in chronic HIV infection were already present early in PHI, and that ART initiation during PHI resulted in only a partial shift of the epigenome to one with more favourable memory characteristics. These findings suggest that although ART initiation during PHI results in significant immune reconstitution, there may be only partial resolution of HIV-related phenotypic and epigenetic changes.

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