HIV-1 integration in microglia (RNA-seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE208047 | GEO | 2023/02/20
REPOSITORIES: GEO
Similar Datasets
Project description:We performed LM-PCR in an infected microglia cell line (C20) to map HIV-1 integration sites. Our aim was to compare the IS obtained through this method with ChIP-seq, ATAC-seq, and RNA-seq data obtained in the uninfected cells, allowing the assessment of integration preferences.
2023-02-20 | GSE206255 | GEO
Project description:We performed ChIP-seq in a microglia cell line (C20) to understand integration patterns of HIV-1. We characterised the uninfected epigenetic cellular landscape in order to assess how integration is affected by distinct chromatin states and to understand the features defining integration-permissible regions.
2023-02-20 | GSE205914 | GEO
Project description:We performed ATAC-seq in a microglia cell line (C20) to assess chromatin accessibility alterations upon HIV-1 infection in latent and active status in comparison with the uninfected status.
2023-02-20 | GSE205807 | GEO
Project description:We performed ChIP-seq in a microglia cell line (C20) upon CTCF-KD and CTCF-NT (wild-type) to understand the impact of CTCF loss on chromatin and HIV-1 integration pattern in the C20 cell line.
2023-02-20 | GSE220859 | GEO
Project description:HIV-1 encounters the hierarchically organized host chromatin to stably integrate and persist in anatomically distinct latent reservoirs. The contribution of genome organization in HIV-1 infection has been largely understudied across different HIV-1 targets. Here we determine HIV-1 integration sites (IS), associate them to chromatin and expression signatures at different genomic scales in a microglia cell model and profile them together with the primary T cell reservoir. HIV-1 insertions into introns of actively transcribed genes with IS hotspots in genic- and super-enhancers, characteristic of blood cells, are maintained in the microglia cell model. Genome organization analysis reveals dynamic CCCTC-binding factor (CTCF) clusters in cells with active and repressed HIV-1 transcription, while CTCF removal impairs viral integration. We identify CTCF-enriched topologically associated domain (TAD) boundaries with signatures of transcriptionally active chromatin as HIV-1 integration determinant in microglia and CD4+ T cells, highlighting the importance of the host genome organization in HIV-1 infection.
2023-01-24 | GSE223638 | GEO
Project description:DNA integration is a defining step in the retroviral life cycle and the basis of stable gene transfer in retrovirus-based gene therapy. Previous studies of integration by HIV-based vectors have shown that integration is not random, but favored in active transcription units. Studies to date have focused on HIV integration in dividing cells, leaving open the question of whether integration target site selection might differ in nondividing cells. According to one idea, division of the host cell might be required for favored integration in transcription units, possibly as a result of chromatin remodeling during DNA replication. Here we have investigated this issue by comparing integration in dividing IMR-90 primary lung fibroblasts to integration in nondividing IMR-90 cells arrested in G1 by serum starvation and contact inhibition. We identified several differences in integration site selection in arrested versus dividing cells, including the frequency of integration in transcription units and in gene-rich regions. However, integration in nondividing cells was in fact more favored in transcription units, contrary to the idea that cell division was important for this bias. These data provide the first view of lentiviral integration in nondividing cells and help constrain models for the mechanism of favored integration in genes. Keywords: comparative genomic analysis, dividing versus non-dividing cells.
2005-11-10 | GSE3555 | GEO
Project description:Distinct integration patterns of different retroviruses have puzzled virologists for over 20 years. The viral integrase (IN), as part of the intasome complex, docks onto the target DNA (tDNA) and catalyzes the insertion of the viral genome into the host chromatin. We identified retroviral IN amino acids directly contacting tDNA bases and affecting the local integration site sequence biases. These residues also determine the propensity of the virus to integrate into flexible tDNA sequences. Remarkably, natural polymorphisms INS119G and INR231G retarget viral integration away from gene dense regions, without affecting the interaction with the lentiviral tethering cofactor LEDGF/p75 (PSIP1). Precisely these variants were associated with rapid disease progression in a chronic HIV-1 subtype C infection cohort. These findings link integration site selection to virulence and viral evolution but also to the host immune response and antiretroviral therapy, since HIV-1 IN119 is under selection by HLA alleles and integrase inhibitors. LEDGF/p75 (PSIP1) ChIP-Seq using A300-848 antibody (recognizes p75 isoform) and input control in primary CD4+ T-cells
2015-01-26 | E-GEOD-61003 | biostudies-arrayexpress
Project description:Distinct integration patterns of different retroviruses have puzzled virologists for over 20 years. The viral integrase (IN), as part of the intasome complex, docks onto the target DNA (tDNA) and catalyzes the insertion of the viral genome into the host chromatin. We identified retroviral IN amino acids directly contacting tDNA bases and affecting the local integration site sequence biases. These residues also determine the propensity of the virus to integrate into flexible tDNA sequences. Remarkably, natural polymorphisms INS119G and INR231G retarget viral integration away from gene dense regions, without affecting the interaction with the lentiviral tethering cofactor LEDGF/p75 (PSIP1). Precisely these variants were associated with rapid disease progression in a chronic HIV-1 subtype C infection cohort. These findings link integration site selection to virulence and viral evolution but also to the host immune response and antiretroviral therapy, since HIV-1 IN119 is under selection by HLA alleles and integrase inhibitors.
2015-01-26 | GSE61003 | GEO
Project description:DNA integration is a defining step in the retroviral life cycle and the basis of stable gene transfer in retrovirus-based gene therapy. Previous studies of integration by HIV-based vectors have shown that integration is not random, but favored in active transcription units. Studies to date have focused on HIV integration in dividing cells, leaving open the question of whether integration target site selection might differ in nondividing cells. According to one idea, division of the host cell might be required for favored integration in transcription units, possibly as a result of chromatin remodeling during DNA replication. Here we have investigated this issue by comparing integration in dividing IMR-90 primary lung fibroblasts to integration in nondividing IMR-90 cells arrested in G1 by serum starvation and contact inhibition. We identified several differences in integration site selection in arrested versus dividing cells, including the frequency of integration in transcription units and in gene-rich regions. However, integration in nondividing cells was in fact more favored in transcription units, contrary to the idea that cell division was important for this bias. These data provide the first view of lentiviral integration in nondividing cells and help constrain models for the mechanism of favored integration in genes. Experiment Overall Design: IMR-90 cells (initially passaged 36 times) were cultured in DMEM with 10% FBS until the cells reached 100% confluence, at which point the medium was substituted to contain only 0.5% FBS. The cells were cultivated for 2 weeks prior to harvesting for RNA extraction. 2 arrays were hybridized, using RNA from 2 independent cell cultures. The data of these growth arrested cells was compared to dividing IMR90 cells (Mitchell et al. 2004. PLoS Biology. 2(8):E234).
2008-06-12 | E-GEOD-3555 | biostudies-arrayexpress
Project description:We report the integration site specificity of Cas1–Cas2 into target plasmid DNA encoding a CRISPR locus. The goal of this study is to determine the effect of IHF on target site selection of Cas1–Cas2.
2016-05-27 | GSE79992 | GEO