Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA326780 | ENA |
REPOSITORIES: ENA
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Project description:Interferon ε (IFNε) is a unique type I IFN that is not induced by pattern-recognition response elements. IFNε is constitutively expressed in mucosal tissues including the female genital mucosa. We show here that IFNε induces an antiviral state in human macrophages that blocks HIV-1 replication. In this work, we examined effects and underlying mechanisms of IFNε in HIV infection of monocyte-derived macrophages (MDMs). We found that IFNε blocked HIV replication in macrophages. It acted on early stages of the HIV life cycle including entry and reverse transcription. It did not appear to operate through known IFN-induced HIV host restriction factors. IFNε induced immune responses in primary macrophages distinct from those induced by IFNα. Importantly, we discovered a novel protective effect of IFNε in primary macrophages against HIV by surging reactive oxygen species (ROS).
2016-10-03 | GSE83716 | GEO
Project description:HIV downregulates interferon stimulated genes in primary macrophages.
| PRJNA178033 | ENA
Project description:Analysis of interferon-stimulated genes (ISGs) in various primary cells and immortalized cell lines, following type 1 interferon (IFN) treatment. Some cell types become resistant to HIV-1 infection following type 1 interferon treatment (such as macrophages, THP-1, PMA-THP-1, U87-MG cells and to a lesser extent, primary CD4+ T cells) while others either become only partially resistant (e.g., HT1080, PMA-U937) or remain permissive (e.g., CEM, CEM-SS, Jurkat T cell lines and U937); for more information see (Goujon and Malim, Journal of Virology 2010) and (Goujon and Schaller et al., Retrovirology 2013). We hypothesized that the anti-HIV-1 ISGs are differentially induced and expressed in restrictive cells compared to permissive cells and performed a whole genome analysis following type 1 IFN treatment in cell types exhibiting different HIV-1 resistance phenotypes. 48 samples; design: 9 cell lines, primary CD4+ T cells and primary macrophages, untreated and IFN-treated; 2 replicate experiments per cell line; 3 replicate experiments per primary cell type
2013-09-13 | E-GEOD-46599 | biostudies-arrayexpress
Project description:Wild type HIV-1 can infect macrophages to establish productive infection without triggering innate immune receptors or type 1 interferon responses that would otherwise restrict virus propagation. We found that HIV-1 capsid mutants that disrupt capsid interactions with two host factors CPSF6 and cyclophillin A do not replicate in macrophages because they do trigger interferon responses. Genome-wide transcriptional profiling was used to compare the repertoire of interferon stimulated genes induced by these capsid mutants after 24Êh with stimulation of macrophages with interferon-beta or with the RNA analogue Poly IC.
2014-02-12 | E-MTAB-1437 | biostudies-arrayexpress
Project description:Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1b, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. HIV-1 induced a primed, proinflammatory state, M1HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches. Affymetrix arrays were used to identify genomic macrophage response to HIV during viral spread in culture. Experiment Overall Design: An HIV-1 spreading infection was established in primary human macrophages. RNA was extracted from both viral- and mock-infected macrophages cultures over 7 days and hybridized to Affymetrix HG-U95Av2 GeneChips for analysis.
2009-01-15 | E-GEOD-13395 | biostudies-arrayexpress
Project description:Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFNγ) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFNγ-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFNγ treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ treatment inhibits genome replication. As IFNγ treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
2015-10-20 | GSE64996 | GEO
Project description:Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFNγ) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFNγ-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFNγ treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ treatment inhibits genome replication. As IFNγ treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
2015-10-20 | GSE64995 | GEO
Project description:Highly Exposed-Seronegatives (HESN) individuals do not contract HIV-1 infection despite long-term exposure; few comprehensive studies examining behavior, mucosal tissue, and peripheral immune parameters in sexually-exposed HESN have been completed. To this end, we assessed rate of condomless vaginal sex, the immune activation status (peripheral blood) and gene expression (ectocervical biopsies) in female cohort of high-risk female sex workers [FSW] (n=50) and non-sex worker women [CG] (n=32) in San Juan, Puerto Rico, USA. Of the 50 FSWs examined only 5 had detectable anti-HIV responses by either HIV gag-specific CD8+ T-Cell responses or mucosal anti-HIV envelope IgG/IgA. FSW had a uniform lower CD38 expression on circulating CD4+ or CD8+ T-Cells (both: p<0.0001:Wilcoxon Rank Sum). Cervical tissue from FSWs had greater levels of CD4+ T-Cell (p=0.040), CD123+ plasmacytoid Dendritic Cells (p=0.013) and CD68+ macrophage infiltrates (p=0.038). Cervical gene expression by RNA microarray indicated that FSW had a gene signature characterized by lower expression of genes associated with leukocyte homing and chemotaxis; partial interferon regulated gene signature; and lower gene expression of genes required for HIV infection such as CD4 and NUP153 indicating a lower mucosal immune activation state and reduced susceptibility to HIV-1 infection within mucosal tissue. Notably, Interferon (IFN)-ε expression was higher in FSW than CG women, as detected by RNA (microarray) and protein (IHC) expression in cervical epithelium. The observed levels of IFNε were associated with the reported frequency of unprotected intercourse. Finally, IFNε was induced by treatment of the ECT1 cell line with seminal fluid, suggesting that semen exposure may contribute to long-term protection. Decreased levels of immune activation and gene expression required for HIV infection along with semen-induced epithelial Interferon ε production within the reproductive tract of FSWs highlight distinct host intrinsic resistance mechanisms that may contribute to long-term HIV seronegative status in spite of high-risk condomless sex.
2019-11-21 | GSE63441 | GEO
Project description:Analysis of interferon-stimulated genes (ISGs) in various primary cells and immortalized cell lines, following type 1 interferon (IFN) treatment. Some cell types become resistant to HIV-1 infection following type 1 interferon treatment (such as macrophages, THP-1, PMA-THP-1, U87-MG cells and to a lesser extent, primary CD4+ T cells) while others either become only partially resistant (e.g., HT1080, PMA-U937) or remain permissive (e.g., CEM, CEM-SS, Jurkat T cell lines and U937); for more information see (Goujon and Malim, Journal of Virology 2010) and (Goujon and Schaller et al., Retrovirology 2013). We hypothesized that the anti-HIV-1 ISGs are differentially induced and expressed in restrictive cells compared to permissive cells and performed a whole genome analysis following type 1 IFN treatment in cell types exhibiting different HIV-1 resistance phenotypes.
2013-09-13 | GSE46599 | GEO
Project description: Not available
| S-EPMC2531291 | biostudies-literature