Dataset Information

IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response.

ABSTRACT: Viral defense at mucosal sites depends on interferons (IFN) and IFN stimulated genes (ISGs), either of which may be constitutively expressed to maintain an "antiviral state" (AVS). However, the mechanisms that govern the AVS are poorly defined. Using a BEAS-2B respiratory epithelial cell line deficient in IRF1, we demonstrate higher susceptibility to infection with vesicular stomatitis virus (VSV) and influenza virus. IRF1-mediated restriction of VSV is IFN-independent, as blockade of types I and III IFNs and JAK-STAT signaling before infection did not affect VSV infection of either parent or IRF1 KO cells. Transcriptome analysis revealed that IRF1 regulates constitutive expression of ~300 genes, including antiviral ISGs: OAS2, BST2, and RNASEL and knockdown of any of these IRF1-dependent genes increased VSV infection. Additionally, IRF1 enhances rapid expression of IFN? and IFN? after stimulation with poly I:C and also regulates ISG expression. Mechanistically, IRF1 enhances recruitment of BRD4 to promotor-enhancer regions of ISGs for rapid expression and maintains levels of histone H3K4me1 for optimal constitutive expression. Finally, IRF1 also regulates constitutive expression of TLR2 and TLR3 and promotes signaling through these pattern recognition receptors (PRR). These data reveal multiple roles for IRF1 toward effective anti-viral responses by maintaining IFN-independent constitutive expression of anti-viral ISGs and supporting early IFN-dependent responses to PRR stimulation.

SUBMITTER: Panda D

PROVIDER: S-EPMC6529937 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response.

Panda Debasis D Gjinaj Erisa E Bachu Mahesh M Squire Erica E Novatt Hilary H Ozato Keiko K Rabin Ronald L RL

Frontiers in immunology 20190515

Viral defense at mucosal sites depends on interferons (IFN) and IFN stimulated genes (ISGs), either of which may be constitutively expressed to maintain an "antiviral state" (AVS). However, the mechanisms that govern the AVS are poorly defined. Using a BEAS-2B respiratory epithelial cell line deficient in IRF1, we demonstrate higher susceptibility to infection with vesicular stomatitis virus (VSV) and influenza virus. IRF1-mediated restriction of VSV is IFN-independent, as blockade of types I an ...[more]

PMID: 31156620

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Project description:Al-Mg-Si series aluminum alloy is a heat-treatment-strengthened alloy. Research on the impact resistance of Al-Mg-Si series aluminum alloy is of great significance to expand its application in engineering. Taking 6082-T6 aluminum alloy as the concrete research object, using the split Hopkinson pressure bar (SHPB) device, the dynamic mechanical response of the material under different temperatures and average strain rates was studied, and the service performance of the material under extreme conditions was determined. The absolute temperature rise was introduced to optimize the existing constitutive model. The results show that when the environment temperature is 298.15~473.15 K under high-speed impact, the internal thermal softening effect of the material is dominant in the competition with the work hardening, resulting in a decrease in the flow stress of the material. Through the analysis of the real stress-strain curve, it was found that the elastic modulus of the material was negatively correlated with the strain rate, negatively correlated with the temperature, and showed an obvious temperature-softening effect. Yield strength was negatively correlated with temperature and positively correlated with strain rate, which showed an obvious strain rate hardening effect. Based on SEM microscopic analysis, it was found that under given conditions, adiabatic shear bands appeared in some samples, and their internal structures demonstrated obvious change. It was judged that when high-speed impact occurs, cracks are induced at the shear bands, and the cracks will continue to develop along the adiabatic shear bands, resulting in many oblique cracks which will gradually become larger and eventually lead to material failure. Finally, based on the model, the strain rate and temperature softening terms were improved, and a rise in adiabatic temperature rise was introduced. The improved model can better describe the strain rate effect of the material and accurately describe its flow stress. It provides a theoretical basis for the engineering application of materials.

Dataset Information

IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response.

Publications

IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response.

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