Expression data from CD8alpha positive dendritic cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE75690 | GEO | 2016/06/10
SECONDARY ACCESSION(S): PRJNA305061
REPOSITORIES: GEO
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Project description:We screened a number of interferon inducible genes that may be involved in impeding HBV replication and found an anti-HBV activity in ISG20. ISG20 is an IFN-inducible 3â??- to 5â??-exonuclease, that degrades DNA and RNA and reduces antigen production in hepatocyte-derived cells A range of candidate genes whose expression was dependent on type I IFN stimulation were identified by gene arrays Total RNA from CD8α+ DCs was extracted from mouse spleens 8h after polyI:C (50 μg) stimulation by RNeasyTM kit. Total RNA (10 μg) from each sample was used to prepare cRNA. Gene expression was analyzed with GeneChipTM
2016-06-10 | E-GEOD-75690 | biostudies-arrayexpress
Project description:Type I interferon-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20 kDa ISG, ISG20, is a nuclear 3'-5'exonuclease with preference for single stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20−/− mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses translation of alphavirus RNAs. Consistent with this observation, the pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20−/− mice compared to wild-type viruses, but not in ISG20 ectopic-expressing cells. Our findings establish an indirect role for ISG20 in the early restriction of RNA virus replication by regulating expressionof other ISGs that inhibit translation and possibly other activities in the replication cycle.
2018-07-01 | GSE115729 | GEO
Project description:Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Cytokine treatments can diminish HBV cccDNA via APOBEC3-mediated deamination. Here we show that overexpression of APOBEC3A alone, however, was not sufficient to reduce cccDNA in HBV-infected cells. This required addition of interferon indicating that cccDNA degradation requires an additional, interferon-stimulated gene (ISG). Transcriptome analyses identified ISG20 as the only type I and II interferon-induced, nucleus-resident protein with annotated nuclease activity. ISG20 expression was detected in human livers in acute, self-limiting but not in chronic hepatitis B. ISG20 depletion abolished the interferon-induced loss of cccDNA, and co-expression of ISG20 and APOBEC3A was sufficient to diminish cccDNA. In conclusion, non-cytolytic HBV cccDNA decline requires induction of a deaminase and nuclease. Our findings highlight that ISGs cooperate for their antiviral function and this cooperativity may be explored for therapeutic targeting.
2021-04-22 | PXD019285 | Pride
Project description:Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus that cannot be targeted by available antivirals. Cytokine treatments can purge cccDNA from the nucleus of infected cells by APOBEC3-mediated deamination. cccDNA levels in HBV-infected cells were not reduced by overexpression of APOBEC3A alone, but only after simultaneous addition of interferon. This indicated the need of an additional, interferon-induced factor (ISG). Microarray analysis identified ISG20 as the only nuclease located to the nucleus induced by type I and II interferons. ISG20 was confirmed to be expressed in acute, self-limiting but not in chronic hepatitis B in human livers. ISG20 knockdown abolished the interferon-induced loss of cccDNA, and co-expression of ISG20 and APOBEC3A was sufficient to diminish cccDNA without further treatment. To conclude, nucleolar ISG20 was identified as the nuclease contributing to interferon-induced purging of HBV cccDNA, opening new avenues for antiviral targeting.
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Project description:ISG20 is an interferon-induced 3'-to-5' RNA exonuclease that acts as a broad antiviral innate defense factor. At present, the features that expose RNA to the action of ISG20 remain unclear. However recent studies have pinpointed to RNA epitranscriptomic modifications as modulators that either expose or protect viral RNAs from ISG20, raising the question as to how cellular RNAs, on which these modifications are abundant, cope with ISG20. To obtain an unbiased perspective on this issue, we used RNAseq to pinpoint to the RNA elements that regulate the balance between susceptibility and resistance to ISG20.
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Project description:Viruses employ various strategies to evade innate immunity. Despite many studies on host or viral gene expression, how the cellular proteome responds to internal or external cues, has not been fully investigated. Using a Hepatitis B Virus (HBV) replication model, we performed proteomic analyses of HBV-replicating cells in G1/S and G2/M phases, as a function of IFN-alpha, providing specific information of how HBV infection, in combination with IFN-alpha, alters the hepatocyte proteome. We identified the conserved LSm (Like-Sm1-8) proteins were differentially expressed as a function of HBV replication and IFN-alpha. Specifically, in G2/M, IFN-alpha increased protein level of LSm1, the unique subunit of cytoplasmic LSm1-7 complex involved in mRNA decay. By contrast, IFN-alpha decreased LSm8, the unique subunit of nuclear LSm2-8 complex, a chaperone of U6 spliceosomal RNA. These results suggest cytoplasmic LSm1-7 has antiviral role, whereas nuclear LSm2-8 complex is pro-viral. Employing HBV replication and infection models, siRNA-mediated knockdown of LSm1 increased the level of all viral RNAs. Conversely, knockdown of LSm8 reduced viral RNA levels, dependent on N6-adenosine methylation (m6A) of the epsilon stem-loop at the 5 end of pre-Core/pregenomic (preC/pg) RNA. Methylated RNA immunoprecipitation (MeRIP) assays demonstrated reduced viral RNA methylation upon LSm8 knockdown, dependent on the m6A modification, suggesting the LSm2-8 complex has a role in mediating this modification. Interestingly, splicing inhibitor Cp028 acting upstream of LSm2-8 complex, suppressed levels of viral RNAs without reducing the m6A modification. This observation suggests Cp028 has novel antiviral effects, likely potentiating IFN-alpha -mediated suppression of HBV biosynthesis.
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Project description:To expand knowledge of the effects of interferon at the proteomic level, we treated HepG2 cells with IFN-alpha and IFN-lambda for 24 hours. HepG2.2.15 cells, a model for HBV infection, were also examined versus controls. MTT assays showed that optimized IFN levels (100 ng/ml) did not induce apoptosis relative to untreated controls. Including controls, more than 6,000 proteins were identified. Five replicates each of IFN-alpha treatment, IFN-lambda treatment, and control were performed, allowing confident identification of differentially expressed proteins. While a number of publications suggest that no interferon effect is evident upon HBV infection, our own results strongly suggest otherwise. Differential alterations of the proteasome were noted when comparing HBV infection against IFN-treatment. We also note that differential effects upon IFN treatment significantly overlapped with transcriptomic datasets when upregulation was examined. However, proteins downregulated upon IFN treatment show little overlap with these transcriptomic datasets.
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