Interferon ε protects primary macrophages against HIV infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83716 | GEO | 2016/10/03
SECONDARY ACCESSION(S): PRJNA326780
REPOSITORIES: GEO
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:HIV is able to outpace the innate immune response, including the response mediated by interferon (IFN), to establish a productive infection. However, monocyte derived macrophages (MDMs) may be protected from HIV infection by treatment with type I IFN before virus exposure. The ability of HIV to modulate the type I IFN-mediated innate immune response when it encounters a cell that has already been exposed to IFN was investigated. To investigate the presence of HIV on an established IFN response, MDMs were subjected to four different conditions: (1) IFN-treated only, (2) IFN-treated followed by HIV infection, (3) HIV infected only, and (4) a mock-treated and mock-infected control. Microarray gene expression analysis was performed on a total of 24 samples derived from the 4 conditions assessed at 3 time points (1, 4 and 8 days following treatment/infection) for both IFN-α2 or -ω. Initially, ISGs were identified as those that were upregulated greater than 2-fold by IFN alone (condition 1) at both Days 4 and 8. Then, the IFN-treated condition was compared to the IFN-treated followed by HIV-infection condition in order to identify those ISGs that were downregulated at least 1.5-fold by the presence of HIV at both days. Assuming that it would be counterproductive for HIV infection by itself to induce the expression of ISGs with putative anti-HIV effects, those ISGs that were upregulated greater than 2-fold in the HIV control were removed. Finally, ISGs that passed these filters and were concordant with both IFN-treatments (IFN-α2 and -ω) were identified and corresponded to the following 8 ISGs: AXL receptor tyrosine kinase (AXL), interferon-alpha inducible protein 27 (IFI27), interferon-induced protein 44 (IFI44), interferon-induced protein 44-like (IFI44L), ISG15, OAS1, OAS3 and XIAP associated factor 1 (XAF1). It should be noted that the IFN-α2 and -ω microarray experiments were performed in different batches but batch effects were not corrected since genes were identified by the filtering approach just described within each batch.
2013-01-01 | E-GEOD-41731 | biostudies-arrayexpress
Project description:HIV is able to outpace the innate immune response, including the response mediated by interferon (IFN), to establish a productive infection. However, monocyte derived macrophages (MDMs) may be protected from HIV infection by treatment with type I IFN before virus exposure. The ability of HIV to modulate the type I IFN-mediated innate immune response when it encounters a cell that has already been exposed to IFN was investigated.
2013-01-01 | GSE41731 | GEO
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
Project description:Temporal changes of the expression levels of the complete human transcriptome during the first 24 hours following infection of IFN-pre-treated macrophages. This approach has allowed us to identify genes involved in the IFN signaling that have an impact on HIV-1 infection of macrophages KEYWORDS: time course Purified primary macrophages were treated with 1000 IU/ml of IFNα2, for 18 hours before infection. Pre-treated macrophages were infected with the Bal strain of HIV-1 at an MOI of 1. Uninfected and untreated cells were used for control. Aliquots of cells (3x106 cells) were taken at 0,2, 4, 8, 16 and 24 hrs after infection for RNA extraction and hybridization on Affymetrix microarrays. *** No CEL file for Sample GSM757646 MDMs CTL at T0
2011-12-01 | E-GEOD-30536 | biostudies-arrayexpress
Project description:Emerging evidence suggests brain-resident myeloid cells, including macrophages and microglia, provide a reservoir for HIV infection in the central nervous system (CNS), and their inflammatory activation is a proposed pathogenic mechanism in HIV-associated neurocognitive disorders (HAND). We investigated whether cannabinoid receptor 2 (CB2), an immunomodulatory receptor expressed in myeloid cells, regulates viral replication and inflammation in HIV-infected macrophages and microglia. Using the synthetic CB2-specific agonist, JWH-133, we found that CB2 activation reduces HIV replication in primary human monocyte-derived macrophages (MDMs) and human iPSC-derived microglia (iMg) at differing doses, corresponding to the basal expression of CNR2 and related endocannabinoid transcripts in each cell type. Direct CB2 agonism via JWH-133 broadly reduced cytokine release from HIV-infected MDMs, but not iMg. RNA-seq revealed that CB2 agonism primarily altered interferon and integrated stress response pathways in MDMs; homeostatic pathways, including synapse maintenance and phagocytosis, were altered in iMg. Further investigation in iMg found NLRP3 inflammasome activation, but not priming, was reduced by CB2 activation. This study identifies key discrepancies in CB2 response between myeloid cell types and implicates CB2-specific agonists as promising candidates for regulation of HIV-associated neuroinflammation.
2025-01-22 | GSE250616 | GEO
Project description:The female reproductive tract (FRT) is vulnerable to sexually transmitted infections and therefore a well-tuned immune surveillance system is crucial for maintaining a healthy FRT. However, our understanding of the factors that impact viral infection of the FRT and the host response are not well understood. In this work, we investigate the role of a hormonally regulated type I interferon, IFN epsilon, in control of Zika virus (ZIKV) infection of the FRT. We demonstrate that IFN epsilon has anti-ZIKV properties using a combination of IFN epsilon KO mice, blockade of endogenous IFN epsilon by neutralising Abs and rescue of IFN epsilon KO mice by recombinant IFN epsilon administered directly to the FRT.
2023-02-14 | GSE223635 | GEO
Project description:The testis is susceptible to viral infections, which can impair fertility. Spermatogenic cells were thought to lack anti-viral defences, including interferon (IFN) or IFN-stimulated gene (ISG) expression. Challenging this dogma, we discovered that interferon-epsilon (IFNɛ), a type-I IFN first identified in female reproductive epithelia, is constitutively expressed by spermatogenic cells and macrophages in mouse and human testes. Moreover, mice lacking IFNɛ are more susceptible to viral epididymo-orchitis. The mechanisms of IFNɛ-mediated anti-viral protection in the testis were examined in this study.
2024-10-18 | GSE253517 | GEO
Project description:The testis is susceptible to viral infections, which can impair fertility. Spermatogenic cells were thought to lack anti-viral defences, including interferon (IFN) or IFN-stimulated gene (ISG) expression. Challenging this dogma, we discovered that interferon-epsilon (IFNɛ), a type-I IFN first identified in female reproductive epithelia, is constitutively expressed by spermatogenic cells and macrophages in mouse and human testes. Moreover, mice lacking IFNɛ are more susceptible to viral epididymo-orchitis. The mechanisms of IFNɛ-mediated anti-viral protection in the testis were examined in this study.
2024-10-18 | GSE252991 | GEO
Project description:HIV establishes long-term latent infection in memory CD4+ T cells, but also establishes sustained long-term productive infection in macrophages, especially in the CNS. To better understand how HIV sustains infection in macrophages, we performed RNAseq analysis after infection of human-monocyte derived macrophages (MDMs) with the brain-derived HIV-1 strain YU2 and compared this with acute infection of CD4+ T cells. HIV infection in MDM and CD4+ T-cells altered many gene transcripts, but with few overlaps between these different cell types. We found interferon pathways upregulated in both MDM and CD4+ T-cells, but with different gene signatures. The interferon-stimulated gene RSAD2/Viperin was among the most upregulated genes following HIV infection in MDMs, but not in CD4+ T-cells. RSAD2/Viperin was induced early after infection with various HIV strains, was sustained over time, and remained elevated in established MDM infection even if new rounds of infection were blocked by antiretroviral treatment. Immunofluorescence microscopy revealed that RSAD2/Viperin was induced strongly in HIV infected cells, as well as in some uninfected neighboring cells, and was frequently localized at junctions between cells. Knockdown of RSAD2/Viperin following establishment of infection in MDMs reduced production of HIV transcripts and viral p24 antigen. This correlated with reduction in the number of multinucleated giant cells, and changes in the histone modifications at the HIV LTR, including loss of histone H3K7ac and H3K9me3, epigenetic marks that we have found associated with HIV in MDMs. RNA-seq transcriptomic analysis of RSAD2/Viperin knockdown during HIV infection of MDMs revealed activation of interferon alpha and gamma pathways and inactivation of Rho GTPase pathways. Taken together, these results suggest that RSAD2/Viperin supports HIV infection in macrophages through multiple mechanisms, potentially including the attenuation of the interferon response.
2024-08-27 | GSE253073 | GEO
Project description:Virus infection induces the production of type I and type II interferons (IFN-I and IFN-II), cytokines that mediate the antiviral response. IFN-I (IFN-a and -b) induces the assembly of ISGF3 (interferon-stimulated gene factor 3), a multimeric transcriptional activation complex comprised of STAT1, STAT2 and IRF9. IFN-II (IFN-g) induces the homodimerization of STAT1 to form the GAF (gamma-activated factor) complex. ISGF3 and GAF bind specifically to distinct regulatory DNA sequences located upstream of IFN-I and II inducible genes, respectively, and activate the expression of distinct set of antiviral genes. The balance between the type I and type II IFN pathways plays a critical role in orchestrating the innate and adaptive immune systems. Here, we show that the phosphorylation of STAT1 by IKKε (IkB-related kinase epsilon) inhibits STAT1 homodimerization, and thus GAF formation, but does not disrupt ISGF3 formation. Therefore, virus and/or IFN-I activation of IKKε suppresses GAF-dependent transcription and promotes ISGF3-dependent transcription. In the absence of IKKε, GAF-dependent transcription is enhanced at the expense of ISGF3-mediated transcription, rendering cells less resistant to infection. We conclude that IKKε plays a critical role in regulating the balance between the IFN-I and IFN-II signaling pathways. ChIP-seq libraries were constructed with an antibody targeting STAT1 from bone marrow macrophages treated with interferon
2011-12-01 | E-GEOD-33913 | biostudies-arrayexpress