Interferon Regulatory Factor 8 (IRF8) Impairs Induction of Interferon Induced with Tetratricopeptide Repeat Motif (IFIT) Gene Family Members

White, Christine L.; Kessler, Patricia M.; Dickerman, Benjamin K.; Ozato, Keiko; Sen, Ganes C.

doi:10.1074/jbc.m115.705467

Cited by 11 publications

(24 citation statements)

References 39 publications

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“…terms related to adaptive host immunity, immune effector expression, and proteoglycan binding such as cathepsin L (CTSL) found to be high expression in pig lung alveolus [ 12 ]. Other upregulated genes of immune interest included genes such as T cell immunoreceptor with Ig and ITIM domains (TIGIT) which is a negative regulator of IL-12 and T-cell regulation, but a positive regulator of IL-10 [ 11 , 13 ]. In all, the 3 dpi results showed upregulation of many anti-viral effector genes such as interferon induced protein 44 (IFI44) that can be activated by interferon regulatory factors [ 11 , 13 ].…”

Section: Resultsmentioning

confidence: 99%

Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

et al. 2020

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Interferon (IFN) cytokines induce an autonomous antiviral state in cells of the infected site to restrict virus spreading and critically regulate overall antiviral response. The antiviral state leads to host protection through expression of hundreds of IFN-stimulated genes that restrict viral infection through multiple mechanisms, for example, directly in viral genome degradation and indirectly through cellular metabolic inhibition. Young pigs were split into four treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV, also known as porcine arterivirus) infected, influenza B virus (IBV) infected, and IBV/PRRSV coinfection. Lung tissue was collected at 3, 5, and 7 days post infection (dpi) for control, PRRSV and IBV/PRRSV coinfection, and at 3 and 5 dpi for IBV. Transcriptomic analysis, using usegalaxy.org tools, was performed against the S.scrofa 11.1 reference genome. Differentially expressed gene (DEG) analysis was carried out using DeSeq2 based on the model treatment + dpi + treatment:dpi + E. Downstream analysis examined the interaction of DEG at each dpi for over-enriched gene ontology (G.O.) terms and pathways. Comparisons of the infected groups vs. the controls yielded a total of (n = 1412) DEGs for the PRRSV group and (n = 1578) for the IBV/PRRSV group across all timepoints. The IBV group had (n = 64) total DEGs across 3 and 5 dpi. Expression data were considered statistically significant based on false discovery rate (FDR) ⫹ 0.1. Venn diagram comparisons of the DEGs across dpi showed that groups shared only 16 DEGs at 3 dpi, no DEGs were shared at 5 dpi, and for 7 dpi, only the PRRSV and IBV/PRRSV groups were compared and shared a total of 43 DEGs. Across the comparisons, differential expression was observed in antiviral genes such as IRF1, MX1, and OAS2. The IBV and IBV/PRRSV groups showed higher expression of antiviral genes at earlier dpi than the PRRSV group. Additionally, downregulated genes from the comparisons clustered around Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways effecting lung development and cellular integrity. Early expression of host IFN and antiviral genes may lead to viral RNA degradation, and assembly and transcription inhibition in the IBV infections. In comparison, expression of antiviral genes in the PRRSV group decreased across time. The decrease may explain why PRRSV infections persist, while IBV clears. Moreover, all infected groups showed prolonged upregulation in neutrophil degranulation pathway activity, possibly exacerbating symptomatic lung lesion pathology seen in these respiratory infections.

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Section: Resultsmentioning

confidence: 99%

Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

et al. 2020

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“…IRF-3 can directly regulate the IFIT gene, which is induced early in the immune response [ 48 ]. It is also indicated that IRF-8 attenuates the induction of interferon-induced by IFIT family members [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Immune-associated biomarkers for early diagnosis of Parkinson’s disease based on hematological lncRNA–mRNA co-expression

Lei

Zhang²,

et al. 2020

Bioscience Reports

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Early stage diagnosis of Parkinson's disease (PD) is challenging without significant motor symptoms. The identification of effective molecular biomarkers as a hematological indication of PD may help improve the diagnostic timeliness and accuracy. In this paper, we analyzed and compared the blood samples of PD and control (CTR) patients to identify the disease-related changes and determine the putative biomarkers for PD diagnosis. Based on the RNA sequencing analysis, differentially expressed genes (DEGs) were identified, and the co-expression network of DEGs was constructed using the weighted correlation network analysis (WGCNA). The analysis leads to the identification of 87 genes that were exclusively regulated in the PD group, whereas 66 genes were significantly increased and 21 genes were significantly decreased in contrast to the control group. The results indicate that the core lncRNA-mRNA co-expression network greatly changes the immune response in PD patients. Specifically, the results showed that PWAR6, LINC00861, AC83843.1, IRF family, IFIT family and CaMK4 may play important roles in the immune system of PD. Based on the findings from this the present study, future research aims at identify novel therapeutic strategies for PD.

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“…In addition, IRF8 can be tyrosine phosphorylated [ 32 , 33 , 34 , 35 ], SUMOylated [ 36 ] and ubiquitinated [ 37 , 38 ]. The DBD, IAD and post-translational modifications of IRF8 all contribute to its transcription-regulatory activities [ 36 , 39 , 40 , 41 ]. Phosphorylation and dephosphorylation can alter the function of IRF8 in innate immune responses and leukemia pathogenesis [ 34 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Interferon regulatory factor 8 regulates caspase-1 expression to facilitate Epstein-Barr virus reactivation in response to B cell receptor stimulation and chemical induction

Zhang

2018

PLoS Pathog

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Interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein (ICSBP), is a transcription factor of the IRF family. IRF8 plays a key role in normal B cell differentiation, a cellular process that is intrinsically associated with Epstein-Barr virus (EBV) reactivation. However, whether IRF8 regulates EBV lytic replication remains unknown. In this study, we utilized a CRISPR/Cas9 genomic editing approach to deplete IRF8 and found that IRF8 depletion dramatically inhibits the reactivation of EBV upon lytic induction. We demonstrated that IRF8 depletion suppresses the expression of a group of genes involved in apoptosis and thus inhibits apoptosis induction upon lytic induction by B cell receptor (BCR) stimulation or chemical induction. The protein levels of caspase-1, caspase-3 and caspase-8 all dramatically decreased in IRF8-depleted cells, which led to reduced caspase activation and the stabilization of KAP1, PAX5 and DNMT3A upon BCR stimulation. Interestingly, caspase inhibition blocked the degradation of KAP1, PAX5 and DNMT3A, suppressed EBV lytic gene expression and viral DNA replication upon lytic induction, suggesting that the reduced caspase expression in IRF8-depleted cells contributes to the suppression of EBV lytic replication. We further demonstrated that IRF8 directly regulates CASP1 (caspase-1) gene expression through targeting its gene promoter and knockdown of caspase-1 abrogates EBV reactivation upon lytic induction, partially through the stabilization of KAP1. Together our study suggested that, by modulating the activation of caspases and the subsequent cleavage of KAP1 upon lytic induction, IRF8 plays a critical role in EBV lytic reactivation.

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Interferon Regulatory Factor 8 (IRF8) Impairs Induction of Interferon Induced with Tetratricopeptide Repeat Motif (IFIT) Gene Family Members

Cited by 11 publications

References 39 publications

Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

Immune-associated biomarkers for early diagnosis of Parkinson’s disease based on hematological lncRNA–mRNA co-expression

Interferon regulatory factor 8 regulates caspase-1 expression to facilitate Epstein-Barr virus reactivation in response to B cell receptor stimulation and chemical induction

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