Interferon ε protects primary macrophages against HIV infection
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83716 | GEO | 2016/10/03
SECONDARY ACCESSION(S): PRJNA326780
REPOSITORIES: GEO
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: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: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
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.
2011-12-14 | GSE34428 | GEO
Project description:HIV-1 infection of monocyte-derived macrophages does not elicit a detectable type I IFN response in vitro, however, previously published data has shown that blocking STAT1 and STAT3 inhibits HIV-1 replication. Here we test to see if low levels of IFN inducible genes are detectable in human monocyte-derived macrophages that have been infected with HIV-1 in vitro.
2018-01-09 | GSE108897 | GEO
Project description:Yeast Saccharomyces cerevisiae has been widely used as a model system for studying genome instability. Here, a heterozygous diploid S. cerevisiae strain DZP2 was generated to determine the genomic alterations induced by DNA polymerase ε. The expression of POL2 was regulated by the GAL1 promoter. In combination of a custom SNP microarray, the patterns of chromosomal instability induced by low Pol ε could be explored at a whole genome level in DZP2. Using this system, we found hundreds-fold higher rate of genomic alterations, including aneuploidy, loss of heterozygosity (LOH), and chromosomal rearrangement. DNA polymerase ε (Pol ε) is one of the three replicative eukaryotic DNA polymerases. Pol ε deficiency leads to genomic instability and multiple human diseases. Here, we explored global genomic alterations in yeast strains with reduced expression of POL2, the gene that encodes the catalytic subunit of Pol ε. Using whole-genome SNP microarray and sequencing, we found that low levels of Pol ε elevated the rates of mitotic recombination and chromosomal aneuploidy by two orders of magnitude. Strikingly, low levels of Pol ε resulted in a contraction of the number of repeats in the rDNA cluster and reduced the length of telomeres. These short telomeres led to an elevated frequency of break-induced replication, resulting in terminal loss of heterozygosity. In addition, low levels of Pol ε increased the rate of single-base mutations by 13-fold by a Pol ζ-dependent pathway. Finally, the patterns of genomic alterations caused by low levels of Pol ε were different from those observed in strains with low levels of the other replicative DNA polymerases Pol α and Pol δ, providing further insights into the different roles of the B-family DNA polymerases in maintaining genomic stability.
2021-10-07 | GSE185365 | GEO
Project description:In order to identify IFNα-induced host factor(s) that might inhibit replication of unadapted chimeric SIV/HIV-1 viruses (SHIVs), we measured IFNα-induced gene expression in immortalized pig-tailed macaque (Ptm) CD4+ lymphocytes. Triplicate cultures of Ptm lymphocytes were left untreated or treated with 1000 U/ml of IFNα. Twenty-four hours later, RNA was isolated, and RNA-seq libraries were prepared for sequencing. A total of 198 genes were found to be significantly differentially expressed (|logFC| ≥ 0.585 & FDR 5%) upon IFNα treatment. 147/198 genes were found to be significantly upregulated and 51/198 genes were found to be significantly downregulated regulated upon IFNα treatment.
2019-06-24 | GSE126594 | GEO