Similar Datasets
Project description:Single Cell RNA Sequencing in Primary CD4 T-Cells infected with HIV, suppressed with ART, and treated with IFNb
2022-06-01 | GSE176386 | GEO
Project description:Latent HIV infection disrupts cell-intrinsic innate immunity
| PRJNA729655 | ENA
Project description:Latent HIV infection disrupts cell-intrinsic innate immunity [scRNA-seq]
| PRJNA736056 | ENA
Project description:HIV-1 virion production is inefficient in cells derived from mice and other rodents. Inefficient production maps, in part, to a species-specific polymorphism in the cellular gene, CCNT1. In human cells, the HIV-1 Tat protein hijacks the positive transcription elongation factor (p-TEFb) complex, composed of CCNT1 and the cellular kinase CDK9, to promote viral transcript elongation and thereby increasing net viral gene expression and virion production. In mouse cells, Tat-dependent viral transcription is poor, reflecting the inability of Tat to engage p-TEFb because of a species-specific tyrosine residue at position 261 in the mouse ortholog of CCNT1. Humans encode a cysteine at the equivalent position which Tat requires for efficient p-TEFb usage. Here, we used CRISPR/Cas9 genome engineering to substitute the native cysteine with the rodent-encoded tyrosine (C261Y) in the human Jurkat T cell line (E6-1 clone). We derived two independent Jurkat T cell clones with all endogenous CCNT1 encoding the C261Y substitution. In an effort to understand net impacts to cellular and viral gene expression, we compared the transcriptomes of uninfected parental Jurkat T cells (E6-1 clone) to the two derived clones (C1 and C2, CCNT1.C261Y).
2023-05-01 | GSE209745 | GEO
Project description:Phosphoproteomics show that the tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFNb pathway
2021-01-15 | MSV000086706 | MassIVE
Project description:Proteome analysis reveals that the tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFNb pathway Proteome
2021-01-15 | MSV000086708 | MassIVE
Project description:PML/TRIM19, the organizer of nuclear bodies (NBs), has been implicated in the antiviral response to diverse RNA and DNA viruses. Several PML isoforms generated from a single PML gene by alternative splicing, share the same N-terminal region containing the RBCC/tripartite motif but differ in their C-terminal sequences. Recent studies of all the PML isoforms reveal the specific functions of each. The knockout of PML renders mice more sensitive to vesicular stomatitis virus (VSV). Here we report that among PML isoforms (PMLI to PMLVIIb), only PMLIII and PMLIV confer resistance to VSV. Unlike PMLIII, whose anti-VSV activity is IFN-independent, PMLIV can act at two stages: it confers viral resistance directly in an IFN-independent manner and also specifically enhances IFN-β production via a higher activation of IRF3, thus protecting yet uninfected cells from oncoming infection. PMLIV SUMOylation is required for both activities. This demonstrates for the first time that PMLIV is implicated in innate immune response through enhanced IFN-β synthesis. Depletion of IRF3 further demonstrates the dual activity of PMLIV, since it abrogated PMLIV-induced IFN synthesis but not PMLIV-induced inhibition of viral proteins. Mechanistically, PMLIV enhances IFN-β synthesis by regulating the cellular distribution of Pin1 (peptidyl-prolyl cis/trans isomerase), inducing its recruitment to PML NBs where both proteins colocalize. The interaction of SUMOylated PMLIV with endogenous Pin1 and its recruitment within PML NBs prevents the degradation of activated IRF3, and thus potentiates IRF3-dependent production of IFN-β. Whereas the intrinsic antiviral activity of PMLIV is specific to VSV, its effect on IFN-β synthesis is much broader, since it affects a key actor of innate immune pathways. Our results show that, in addition to its intrinsic anti-VSV activity, PMLIV positively regulates IFN-β synthesis in response to different inducers, thus adding PML/TRIM19 to the growing list of TRIM proteins implicated in both intrinsic and innate immunity.
| S-EPMC3937294 | biostudies-literature
Project description:Innate immunity is a theme of increasing interest for HIV research. However, the term is overstretched to cover biological barriers, cellular systems, soluble factors, signaling pathways, and effectors and is inconsistently applied. A clearer semantic classification of the components of innate immunity is needed, which will have direct relevance to the interpretation of human genome variation. Here, we discuss genomic approaches that can assist in re-defining the perimeter of innate immunity. We place particular emphasis on the characteristics of effectors of the intracellular defense against HIV and other pathogens.
| S-EPMC3732074 | biostudies-literature
Project description:Nitazoxanide (Alinia(®), NTZ) and tizoxanide (TIZ), its active circulating metabolite, belong to a class of agents known as thiazolides (TZD) endowed with broad anti-infective activities. TIZ and RM-4848, the active metabolite of RM-5038, were shown to stimulate innate immunity in vitro. Because natural resistance to HIV-1 infection in HIV-exposed seronegative (HESN) individuals is suggested to be associated with strong innate immune responses, we verified whether TIZ and RM-4848 could reduce the in vitro infectiousness of HIV-1. Peripheral blood mononuclear cells (PBMCs) from 20 healthy donors were infected in vitro with HIV-1BaL in the presence/absence of TIZ or RM4848. HIV-1 p24 were measured at different timepoints. The immunomodulatory abilities of TZD were evaluated by the expression of type I IFN pathway genes and the production of cytokines and chemokines. TZD drastically inhibited in vitro HIV-1 replication (>87%). This was associated with the activation of innate immune responses and with the up-regulation of several interferon-stimulated genes (ISGs), including those involved in cholesterol pathway, particularly the cholesterol-25 hydroxylase (CH25H). TZD inhibition of HIV-1 replication in vitro could be due to their ability to stimulate potent and multifaceted antiviral immune responses. These data warrant the exploration of TZD as preventive/therapeutic agent in HIV infection.
| S-EPMC4890011 | biostudies-other
Project description:A prominent obstacle to HIV eradication in seropositive individuals is the viral persistence in latent reservoir cells, which constitute an HIV sanctuary out of reach of highly active antiretroviral therapies. Thus, the study of molecular mechanisms governing latency is a very active field that aims at providing solutions to face the reservoirs issue. Since the past 15 years, another major field in HIV biology focused on the discovery and study of restriction factors that shape intrinsic immunity, while engaging in a molecular battle against HIV. Some of these restrictions factors act at early stages of the virus life cycle, alike SAMHD1 antagonized by the viral protein Vpx, while others are late actors. Until recently, no such factor was identified in the nucleus and found active at the level of provirus expression, a crucial step where latency may take place. Today, two studies highlight Human Silencing Hub (HUSH) as a potential restriction factor that controls viral expression and is antagonized by Vpx. This Review discusses HUSH restriction in the light of the actual knowledge of intrinsic immunity and HIV latency.
| S-EPMC6379475 | biostudies-literature