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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/28087593/norovirus-mediated-modification-of-the-translational-landscape-via-virus-and-host-induced-cleavage-of-translation-initiation-factors
#1
Edward Emmott, Frederic Sorgeloos, Sarah L Caddy, Surender Vashist, Stanislav Sosnovtsev, Richard Lloyd, Kate Heesom, Nicolas Locker, Ian Goodfellow
Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087453/the-impact-of-isgylation-during-mycobacterium-tuberculosis-infection-in-mice
#2
Jacqueline M Kimmey, Jessica A Campbell, Leslie A Weiss, Kristen J Monte, Deborah J Lenschow, Christina L Stallings
Mycobacterium tuberculosis infection results in 1.5 million deaths annually. Type I interferon (IFN) signaling through its receptor IFNAR correlates with increased severity of disease, although how this increases susceptibility to M. tuberculosis remains uncertain. ISG15 is one of the most highly induced interferon stimulated genes (ISGs) during M. tuberculosis infection. ISG15 functions by conjugation to target proteins (ISGylation), by noncovalent association with intracellular proteins, and by release from the cell...
January 10, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28087229/disease-associated-mutations-identify-a-novel-region-in-human-sting-necessary-for-the-control-of-type-i-interferon-signaling
#3
Isabelle Melki, Yoann Rose, Carolina Uggenti, Lien Van Eyck, Marie-Louise Frémond, Naoki Kitabayashi, Gillian I Rice, Emma M Jenkinson, Anaïs Boulai, Nadia Jeremiah, Marco Gattorno, Sefano Volpi, Olivero Sacco, Suzanne W J Terheggen-Lagro, Harm A W M Tiddens, Isabelle Meyts, Marie-Anne Morren, Petra De Haes, Carine Wouters, Eric Legius, Anniek Corveleyn, Frederic Rieux-Laucat, Christine Bodemer, Isabelle Callebaut, Mathieu P Rodero, Yanick J Crow
BACKGROUND: Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI). OBJECTIVES: We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease...
January 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28079476/mimiviruses-and-the-human-interferon-system-viral-evasion-of-classical-antiviral-activities-but-inhibition-by-a-novel-interferon-%C3%AE-regulated-immunomodulatory-pathway
#4
Gabriel Magno de Freitas Almeida, Lorena C Ferreira Silva, Philippe Colson, Jonatas Santos Abrahao
In this review we discuss the role of mimiviruses as potential human pathogens focusing on clinical and evolutionary evidence. We also propose a novel antiviral immunomodulatory pathway controlled by interferon-β (IFN-β) and mediated by immune-responsive gene 1 (IRG1) and itaconic acid, its product. Acanthamoeba polyphaga Mimivirus (APMV) was isolated from amoebae in a hospital while investigating a pneumonia outbreak. Mimivirus ubiquity and role as protist pathogens are well understood, and its putative status as a human pathogen has been gaining strength as more evidence is being found...
January 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#5
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077645/herpes-simplex-virus-1-abrogates-cgas-sting-mediated-cytosolic-dna-sensing-pathway-via-its-virion-host-shutoff-protein-ul41
#6
Chenhe Su, Chunfu Zheng
: Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor capable of detecting microbial DNA and activating the adaptor protein stimulator of interferon genes (STING), leading to interferon (IFN) production and host antiviral responses. Cells exhibited reduced type I IFN production in response to cytosolic DNA in the absence of cGAS. Although cGAS/STING-mediated DNA-sensing signal is crucial for host defense against many viruses, especial for DNA viruses, few viral components have been identified to specifically target this signaling pathway...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077641/chikungunya-influenza-nipah-and-semliki-forest-chimeric-viruses-with-vesicular-stomatitis-virus-actions-in-the-brain
#7
Anthony N van den Pol, Guochao Mao, Anasuya Chattopadhyay, John K Rose, John N Davis
: Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here we test 4 chimeric viruses in the brain including those in which glycoprotein genes from Nipah, chikungunya, or influenza H5N1 viruses were substituted for the VSV glycoprotein gene...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077630/mavs-is-essential-for-primary-cd4-t-cell-immunity-but-not-for-recall-t-cell-responses-following-an-attenuated-west-nile-virus-infection
#8
Huanle Luo, Evandro Winkelmann, Guorui Xie, Rong Fang, Bi-Hung Peng, Li Li, Helen M Lazear, Slobodan Paessler, Michael S Diamond, Michael Gale, Alan D Barrett, Tian Wang
: The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral-signaling (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the NS4B-P38G vaccine...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077314/biological-or-pharmacological-activation-of-protein-kinase-c-alpha-constrains-hepatitis-e-virus-replication
#9
Wenshi Wang, Yijin Wang, Yannick Debing, Xinying Zhou, Yuebang Yin, Lei Xu, Elena Herrera Carrillo, Johannes H Brandsma, Raymond A Poot, Ben Berkhout, Johan Neyts, Maikel P Peppelenbosch, Qiuwei Pan
Although hepatitis E has emerged as a global health issue, there is limited knowledge of its infection biology and no FDA-approved medication is available. Aiming to investigate the role of protein kinases in hepatitis E virus (HEV) infection and to identify potential antiviral targets, we screened a library of pharmacological kinase inhibitors in a cell culture model, a subgenomic HEV replicon containing luciferase reporter. We identified protein kinase C alpha (PKCα) as an essential cell host factor restricting HEV replication...
January 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28075448/microarray-analysis-of-circular-rna-expression-patterns-in-polarized-macrophages
#10
Yingying Zhang, Yao Zhang, Xueqin Li, Mengying Zhang, Kun Lv
Circular RNAs (circRNAs) are generated from diverse genomic locations and are a new player in the regulation of post-transcriptional gene expression. Recent studies have revealed that circRNAs play a crucial role in fine-tuning the level of microRNA (miRNA)-mediated regulation of gene expression by sequestering miRNAs. The interaction of circRNAs with disease-associated miRNAs suggests that circRNAs are important in the pathology of disease. However, the effects and roles of circRNAs in macrophage polarization have yet to be explored...
January 11, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28073693/crosstalk-between-cytoplasmic-rig-i-and-sting-sensing-pathways
#11
REVIEW
Alessandra Zevini, David Olagnier, John Hiscott
Detection of evolutionarily conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected...
January 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28070326/effects-of-cranberry-extracts-on-gene-expression-in-thp-1-cells
#12
Daniel B Hannon, Jerry T Thompson, Christina Khoo, Vijaya Juturu, John P Vanden Heuvel
Cranberry contains high levels of nutrients and bioactive molecules that have health-promoting properties. The purpose of the present studies was to determine if cranberry extracts (CEs) contain phytochemicals that exert anti-inflammatory effects. The human monocytic cell line THP-1 was treated with two CEs (CE and 90MX) and subsequently challenged with Lipopolysaccharides (LPS). Tumor necrosis factor α (TNF α) expression was decreased in the CE-treated cells, indicative of an anti-inflammatory effect. Gene expression microarrays identified several immune-related genes that were responsive to CEs including interferon-induced protein with tetratricopeptide repeats 1 and 3 (IFIT 1 and 3), macrophage scavenger receptor 1 (MSR1) and colony-stimulating factor 2 (CSF2)...
January 2017: Food Science & Nutrition
https://www.readbyqxmd.com/read/28069950/chronic-innate-immune-activation-of-tbk1-suppresses-mtorc1-activity-and-dysregulates-cellular-metabolism
#13
Maroof Hasan, Vijay K Gonugunta, Nicole Dobbs, Aktar Ali, Guillermo Palchik, Maria A Calvaruso, Ralph J DeBerardinis, Nan Yan
Three-prime repair exonuclease 1 knockout (Trex1(-/-)) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1(-/-) mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069942/a-paradox-of-transcriptional-and-functional-innate-interferon-responses-of-human-intestinal-enteroids-to-enteric-virus-infection
#14
Kapil Saxena, Lukas M Simon, Xi-Lei Zeng, Sarah E Blutt, Sue E Crawford, Narayan P Sastri, Umesh C Karandikar, Nadim J Ajami, Nicholas C Zachos, Olga Kovbasnjuk, Mark Donowitz, Margaret E Conner, Chad A Shaw, Mary K Estes
The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28064541/the-role-of-ifi35-in-lupus-nephritis-and-related-mechanisms
#15
Lihua Zhang, Honglin Zhu, Yisha Li, Xiaodan Dai, Bin Zhou, Quanzhen Li, Xiaoxia Zuo, Hui Luo
OBJECTIVES: It's reported that multiple genes in the IFN-γ/STAT1 pathway were hypomethylated and associated with the pathogenesis of lupus nephritis (LN). Our previous study using microarray analysis suggested that interferon induced 35-kDa protein (IFI35) was hypomethylated and increased in LN. However, the role of IFI35 in LN and related mechanism remains to be elucidate. METHODS: The expressions of IFNγR, STAT1, IFI35 and MBD2 in the human kidneys tissues was detected by real-time PCR and western blot...
January 9, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28062499/role-of-kca3-1-channels-in-macrophage-polarization-and-its-relevance-in-atherosclerotic-plaque-instability
#16
Rende Xu, Chenguang Li, Yizhe Wu, Li Shen, Jianying Ma, Juying Qian, Junbo Ge
OBJECTIVE: Emerging evidence indicates that proinflammatory macrophage polarization imbalance plays a key role in atherosclerotic plaque progression and instability. The calcium-activated potassium channel KCa3.1 is critically involved in macrophage activation and function. However, the role of KCa3.1 in macrophage polarization is unknown. This study investigates the potential role of KCa3.1 in transcriptional regulation in macrophage polarization and its relationship to plaque instability...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062222/absent-in-melanoma-2-proteins-in-sle
#17
REVIEW
Divaker Choubey, Ravichandran Panchanathan
Type I interferons (IFN-α/β)-inducible PYRIN and HIN domain-containing protein family includes Absent in Melanoma 2 (murine Aim2 and human AIM2), murine p202, and human PYRIN-only protein 3 (POP3). The generation of Aim2-deficient mice indicated that the Aim2 protein is essential for inflammasome activation, resulting in the secretion of interleukin-1β (IL-1β) and IL-18 and cell death by pyroptosis. Further, Aim2-deficiency also increased constitutive expression of the IFN-β and expression of the p202 protein...
January 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28060952/trim25-enhances-the-antiviral-action-of-zinc-finger-antiviral-protein-zap
#18
Melody M H Li, Zerlina Lau, Pamela Cheung, Eduardo G Aguilar, William M Schneider, Leonia Bozzacco, Henrik Molina, Eugen Buehler, Akinori Takaoka, Charles M Rice, Dan P Felsenfeld, Margaret R MacDonald
The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits...
January 6, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28058287/impact-of-il-27-on-hepatocyte-antiviral-gene-expression-and-function
#19
Narayan Ramamurthy, Sara Boninsegna, Rebecca Adams, Natasha Sahgal, Helen Lockstone, Dilair Baban, Emanuele Marchi, Paul Klenerman
Background: Interleukin (IL)-27 is a member of the IL-6/IL-12 family of cytokines. It is a potent cytokine, with potential antiviral impact, and has been shown to play a role in modulating functions of diverse cell types, including Th1, Th2, and NK and B cells, demonstrating both pro- and anti-inflammatory roles.  In hepatocytes, it is capable of inducing signal transducer and activator of transcription (STAT)1, STAT3 and interferon-stimulated genes. Methods: To address its role in viral hepatitis, the antiviral activity of IL-27 against hepatitis C virus (HCV) and hepatitis B virus (HBV) was tested in vitro using cell-culture-derived infectious HCV (HCVcc) cell culture system and the HepaRG HBV cell culture model...
November 17, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/28056062/antiviral-efficacy-and-host-immune-response-induction-during-sequential-treatment-with-sb-9200-followed-by-entecavir-in-woodchucks
#20
Manasa Suresh, Kyle E Korolowicz, Maria Balarezo, Radhakrishnan P Iyer, Seetharamaiyer Padmanabhan, Dillon Cleary, Rayomand Gimi, Anjaneyulu Sheri, Changsuek Yon, Bhaskar V Kallakury, Robin D Tucker, Nezam Afdhal, Stephan Menne
SB 9200, an orally bioavailable dinucleotide, activates the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) causing the induction of the interferon (IFN) signaling cascade for antiviral defense. The present study evaluated the overall antiviral response in woodchucks upon induction of immune response, first with SB 9200 followed by Entecavir (ETV) versus reduction of viral burden with ETV followed by SB 9200 immunomodulation...
2017: PloS One
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