Ontology highlight
ABSTRACT:
PROVIDER: PRJNA668519 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are delineated with super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional activity are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
2019-08-21 | GSE134382 | GEO
Project description:HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional status are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
2018-11-22 | GSE122826 | GEO
Project description:HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional status are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
2018-11-21 | GSE122735 | GEO
Project description:Mucosa-associated invariant T (MAIT) cells recognize microbial-derived riboflavin metabolites presented by the evolutionarily conserved MR1 molecule. Their persistent loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we explore MAIT cell dynamics in the critical acute stages of HIV-1 infection for the first time
2019-02-20 | GSE126752 | GEO
Project description:The high prevalence of cognitive alterations in persons with HIV (PWH) despite effective antiretroviral therapy (ART) is associated with sustained neuroinflammation. Here, we uncover the signaling pathways that are essential for persistent immune activation and might underly development of HIV associated Neurocognitive Disorder (HAND). We analyze the brain proteome from PWH on ART during HAND progression. We observe that 73.3% of the significantly upregulated proteins in brains from PWH and HAND (compared to PWH with normal cognition) belong to immune pathways. Among them, 36.4% of upregulated innate immune-related proteins are within the type I interferon (IFN-I) signaling, suggesting that persistent IFN-I activation is central to HAND-associated brain immune activation. Single cell (sc)RNA-seq analysis confirmed that FN-I occurs mainly in astrocytes during acute HIV infection in the microglia-containing organoid (MCO) model of HIV infection and persistent in microglia in the brain of PLWH on ART. Of note, IFN-I persistence is independent of HIV status but associated with the induction of human endogenous retroviruses-W (HERV-W) Env during HAND progression after initial HIV infection and its associated immune activation. When induced, HERV-W Env directly activates IFN-I signaling in astrocytes, but not in microglia. Together, IFN-I signaling may be initiated directly in the astrocytes after acute HIV infection then sustained in the microglia during ART. IFN-I persists due to expression of HERV-W Env, thereby contributing to the persistent immune activation in the HAND brain on ART, independent of HIV and insensitive to ART. Our data link the neuroinflammation of persistent IFN-I signaling to the HAND brain on ART.
2024-05-25 | GSE233717 | GEO
Project description:Retroviral integration is mediated by a unique enzymatic process shared by all retroviruses and retrotransposons. During integration, double-stranded linear viral DNA is inserted into the host genome in a process catalyzed by viral-encoded integrase. However, host cell defenses against HIV-1 integration are not clear. This study identifies -catenin-like protein 1 (CTNNBL1) as a potent inhibitor of HIV-1 integration via association with viral IN and its cofactor, lens epithelium-derived growth factor/p75. CTNNBL1 overexpression blocks HIV-1 integration and inhibits viral replication, whereas CTNNBL1 depletion significantly upregulates HIV-1 integration into the genome of various target cells. Further, CTNNBL1 expression is downregulated in CD4+ T cells by activation, and CTNNBL1 depletion also facilitates HIV-1 integration in resting CD4+ T cells. Thus, host cells may employ CTNNBL1 to inhibit HIV-1 integration into the genome. This finding suggests a strategy for the treatment of HIV infections.
2022-02-24 | PXD031853 | iProX
Project description:Using novel methods for mapping U/A base pairs in HIV DNA, we find that HIV proviruses within infected monocytes and macrophages contain high levels of U/A base pairs arising from the high levels of dUTP present during reverse transcription in these cells. Although U/A pairs retain the coding information of T/A pairs, they are the substrate for the nuclear uracil base excision repair (UBER) machinery that effectively degrades most of the uracilated viral DNA at the pre-integration stage of infection. Uracilated proviruses that successfully integrate either retain the uracils, undergo U/A T/A repair, or experience catastrophic mutagenesis induced by cytokine stimulated error-prone repair. Uracil is abundant in proviruses isolated from genomic DNA of short-lived blood monocytes, but not T cells, of HIV infected blood donors who show complete drug suppression plasma virus. This suggests that monocytes are recently infected by coming into contact with persistent virus producing cells in one or more tissue reservoirs. Data for HIV lockdown of Illumina libraries of MDM cells post viral infection with and without UDG treatment as compared to HT29-ugi cells treated with RTX.
2016-01-19 | E-GEOD-76091 | biostudies-arrayexpress
Project description:Untreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection. Experiment Overall Design: A total of 52 patients were analyzed: 10 patients unaffected, 18 patients with asymptomatic stages of AIDs, 16 patients with acute stages of AIDs, and 8 patients with AIDs.
2009-06-08 | E-GEOD-16363 | biostudies-arrayexpress
Project description:Some viruses have established an equilibrium with their host. African green monkeys (AGM) display persistent high viral replication in blood and intestine during Simian immunodeficiency virus (SIV) infection but resolve systemic inflammation after acute infection and lack intestinal immune or tissue damage during chronic infection. We show that NKG2 a/c + CD8 + T cells increase in blood and intestine of AGM in response to SIVagm infection in contrast to SIVmac infection in macaques, the latter modeling HIV infection. NKG2 a/c + CD8 + T cells were not expanded in lymph nodes and CXCR5 + NKG2 a/c + CD8 + T cell frequencies further decreased after SIV infection. Genome-wide transcriptome analysis of NKG2 a/c + CD8 + T cells from AGM revealed the expression of NK cell receptors, and of molecules with cytotoxic effector, gut homing, immunoregulatory and gut barrier function, including CD73. NKG2 a/c + CD8 + T cells correlated negatively with IL-23 in the intestine during SIVmac infection. The data suggest a potential regulatory role of NKG2 a/c + CD8 + T cells in intestinal inflammation during SIV/HIV infections.
2021-03-11 | E-MTAB-8664 | biostudies-arrayexpress
Project description:Macrophages play a crucial role in HIV-1 pathogenesis. Toll-like receptors (TLRs) are fundamental for innate and adaptive immune responses, but their role in HIV-1 infection is still incompletely understood. The TLR3 and TLR4 ligands poly(I:C) and LPS are known to modulate HIV-1 infection of and replication in monocyte-derived macrophages (MDMs), but the mechanism is incompletely understood. We found that MDMs stimulation with poly(I:C) or LPS abrogated infection by CCR5-using, macrophage-tropic HIV-1, or by VSV-G-pseudotyped HIV-1 virions, while TLR7 and TLR9 agonists Imiquimod and CpG only reduced infection to varying extent. Suppression of infection, or lack thereof, did not correlate with differential effects on CD4 or CCR5 expression, type I interferon induction, or production of pro-inflammatory cytokines. Furthermore, integrated pro-viruses were readily detected in unstimulated, TLR7- and TLR9-stimulated cells, but not in TLR3- or TLR4-stimulated MDMs, suggesting the alteration of post-entry, pre-integration event(s). MicroRNA (miRNA) microarray and real time PCR demonstrated increased miR-155 levels in MDMs upon TLR3/4, but not TLR7, stimulation, and a miR-155 inhibitor partially restored infectivity in poly(I:C)-stimulated MDMs. Finally, miR-155 over-expression in MDMs and cell lines remarkably diminished HIV-1 infection, inducing an accumulation of late reverse transcription products, concurrently with a decrease in mRNA levels of several HIV-1 dependency factors involved in nuclear import of pre-integration complexes. Our results suggest that miR-155 may target mRNA(s) for host cell protein(s) that either participate in or facilitate post-entry, pre-integration events, resulting in severely diminished HIV-1 infection. miRNA profiles were investigated in total RNA isolated from unstimulated and TLR3-, TLR4- and TLR7-stimulated human MDMs from a single normal donor
2011-12-14 | E-GEOD-34428 | biostudies-arrayexpress