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https://www.readbyqxmd.com/read/28819164/hypoxia-triggers-ifn-i-production-in-muscle-implications-in-dermatomyositis
#1
Noemí De Luna, Xavier Suárez-Calvet, Cinta Lleixà, Jordi Diaz-Manera, Montse Olivé, Isabel Illa, Eduard Gallardo
Dermatomyositis is an inflammatory myopathy characterized by symmetrical proximal muscle weakness and skin changes. Muscle biopsy hallmarks include perifascicular atrophy, loss of intramuscular capillaries, perivascular and perimysial inflammation and the overexpression of IFN-inducible genes. Among them, the retinoic-acid inducible gene 1 (RIG-I) is specifically overexpressed in perifascicular areas of dermatomyositis muscle. The aim of this work was to study if RIG-I expression may be modulated by hypoxia using an in vitro approach...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818792/regulation-of-type-i-interferon-responses-by-mitochondria-derived-reactive-oxygen-species-in-plasmacytoid-dendritic-cells
#2
Zsofia Agod, Tünde Fekete, Marietta M Budai, Aliz Varga, Attila Szabo, Hyelim Moon, Istvan Boldogh, Tamas Biro, Arpad Lanyi, Attila Bacsi, Kitti Pazmandi
Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major producers of type I interferons (IFN), are the key coordinators of antiviral immunity. The early phase of type I IFN production in pDCs is mediated by endosomal Toll-like receptors (TLRs), whereas the late phase of IFN response can also be triggered by cytosolic retinoic acid-inducible gene-I (RIG-I), expression of which is induced upon TLR stimulation...
July 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/28815217/deletion-of-cytoplasmic-double-stranded-rna-sensors-does-not-uncover-viral-small-interfering-rna-production-in-human-cells
#3
Susan Schuster, Lotte E Tholen, Gijs J Overheul, Frank J M van Kuppeveld, Ronald P van Rij
Antiviral immunity in insects and plants is mediated by the RNA interference (RNAi) pathway in which viral long double-stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer enzymes. Although this pathway is evolutionarily conserved, its involvement in antiviral defense in mammals is the subject of debate. In vertebrates, recognition of viral RNA induces a sophisticated type I interferon (IFN)-based immune response, and it has been proposed that this response masks or inhibits antiviral RNAi...
July 2017: MSphere
https://www.readbyqxmd.com/read/28811654/characterization-of-the-mollusc-rig-i-mavs-pathway-reveals-an-archaic-antiviral-signalling-framework-in-invertebrates
#4
Baoyu Huang, Linlin Zhang, Yishuai Du, Fei Xu, Li Li, Guofan Zhang
Despite the mitochondrial antiviral signalling protein (MAVS)-dependent RIG-I-like receptor (RLR) signalling pathway in the cytosol plays an indispensable role in the antiviral immunity of the host, surprising little is known in invertebrates. Here we characterized the major members of RLR pathway and investigated their signal transduction a Molluscs. We show that genes involved in RLR pathway were significantly induced during virus challenge, including CgRIG-I-1, CgMAVS, CgTRAF6 (TNF receptor-associated factor 6), and CgIRFs (interferon regulatory factors...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808965/rna-pamps-as-molecular-tools-for-evaluating-rig-i-function-in-innate-immunity
#5
Renee C Ireton, Courtney Wilkins, Michael Gale
Pathogen recognition receptors (PRR)s and their cognate pathogen-associated molecular pattern (PAMP) represent the basis of innate immune activation and immune response induction driven by the host-pathogen interaction that occurs during microbial infection in humans and other animals. For RNA virus infection such as hepatitis C virus (HCV) and others, specific motifs within viral RNA mark it as nonself and visible to the host as a PAMP through interaction with RIG-I-like receptors including retinoic inducible gene-I (RIG-I)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807907/an-original-chemical-series-of-pyrimidine-biosynthesis-inhibitors-that-boost-the-antiviral-interferon-response
#6
Marianne Lucas-Hourani, Daniel Dauzonne, Hélène Munier-Lehmann, Samira Khiar, Sébastien Nisole, Julien Dairou, Olivier Helynck, Philippe V Afonso, Frédéric Tangy, Pierre-Olivier Vidalain
De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit a broad-spectrum antiviral activity as well as immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28806404/rig-i-and-il-6-are-negative-feedback-regulators-of-sting-induced-by-double-stranded-dna
#7
Xueling Wu, Jun Yang, Tao Na, Kehua Zhang, Andrew M Davidoff, Bao-Zhu Yuan, Youchun Wang
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA)...
2017: PloS One
https://www.readbyqxmd.com/read/28804020/porcine-2-5-oligoadenylate-synthetase-2-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication-in%C3%A2-vitro
#8
Mengmeng Zhao, Bo Wan, Huawei Li, Jian He, Xinxin Chen, Linjian Wang, Yinbiao Wang, Sha Xie, Songlin Qiao, Gaiping Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) is acknowledged a fulminating infectious pathogen affecting the pig farming industry, and current vaccines and drugs could hardly inhibit this virus. The 2', 5'-oligoadenylate synthetase (OASs) have antiviral activities, but the role(s) played by porcine OAS2 in protection against PRRSV infection are unknown. Here we found that endogenous expression of the porcine OAS2 gene could be promoted by interferon (IFN)-beta or PRRSV infection in porcine alveolar macrophages...
August 10, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28794402/dec1-negatively-regulates-the-expression-of-cxcl10-and-ccl5-induced-by-poly-ic-in-normal-human-mesangial-cells
#9
Qiang Liu, Tadaatsu Imaizumi, Keishu Murakami, Hiroshi Tanaka, Yunyan Wu, Tadashi Yoshizawa, Satoko Morohashi, Hiroko Seino, Hiroshi Kijima
The functions of differentiated embryonic chondrocyte gene (DEC) 1, a basic helix-loop-helix (bHLH) transcription factor, have been reported to be associated with the regulation of mammalian circadian rhythms, differentiation of chondrocytes and skeletal muscles, apoptosis, hypoxia-induced reactions and epithelial mesenchymal transition. Our previous report showed that another bHLH transcription factor DEC2 constitutes a negative feedback loop in Toll-like receptor 3 (TLR3)/interferon (IFN)-β-mediated inflammatory responses in human mesangial cells...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28794024/highly-pathogenic-new-world-arenavirus-infection-activates-the-pattern-recognition-receptor-pkr-without-attenuating-virus-replication-in-human-cells
#10
Cheng Huang, Olga A Kolokoltsova, Elizabeth J Mateer, Takaaki Koma, Slobodan Paessler
The arenavirus family consists of several highly pathogenic viruses including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junín virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. NW JUNV and MACV infections readily induce an IFN response in human cells, while OW LASV infection usually triggers an undetectable or weak IFN response. JUNV induces IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs during infection and activates IFN response...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28776416/synthetic-agonists-of-nod-like-rig-i-like-and-c-type-lectin-receptors-for-probing-the-inflammatory-immune-response
#11
Amy E Nielsen, Joseph D Hantho, Rock J Mancini
Synthetic agonists of innate immune cells are of interest to immunologists due to their synthesis from well-defined materials, optimized activity, and monodisperse chemical purity. These molecules are used in both prophylactic and therapeutic contexts from vaccines to cancer immunotherapies. In this review we highlight synthetic agonists that activate innate immune cells through three classes of pattern recognition receptors: NOD-like receptors, RIG-I-like receptors, and C-type lectin receptors. We classify these agonists by the receptor they activate and present them from a chemical perspective, focusing on structural components that define agonist activity...
August 4, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28768856/non-encapsidated-5-copy-back-defective-interfering-genomes-produced-by-recombinant-measles-viruses-are-recognized-by-rig-i-and-lgp2-but-not-mda5
#12
Marie Mura, Chantal Combredet, Valérie Najburg, Raul Y Sanchez David, Frédéric Tangy, Anastassia V Komarova
Attenuated Measles virus (MV) is one of the most effective and safe vaccine available, making it an attractive candidate vector to prevent other infectious diseases. Yet the great capacity of this vaccine still needs to be understood at the molecular level. MV vaccine strains have different type-I interferon-inducing abilities, that partially depend on the presence of 5' copy-back defective interfering genomes (DI-RNAs). DI-RNAs are pathogen associated molecular patterns recognized by RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) that activate innate immune signalling and shape the adaptive immune response...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28762092/socs1-and-pattern-recognition-receptors-tlr9-and-rig-i-novel-haplotype-associations-in-egyptian-fibrotic-cirrhotic-patients-with-hcv-genotype-4
#13
Samar S Youssef, Nadia M Hamdy
In this paper we explore the role of suppressor of cytokine signaling 1 (SOCS1) (rs243327), the regulator of toll-like receptor-9 (TLR9) (rs352140), retinoic acid inducible gene-I (RIG-I) (rs669260), and cluster of differentiation 152 (CD152) (rs231776) in fibrotic/cirrhotic patients. Single nucleotide polymorphisms (SNPs) within these genes as well as haplotype analyses were performed on a cohort of 120 Egyptian fibrotic patients. Fibrosis had progressed from HCV genotype 4 infections. Using RT-PCR, SNPs were evaluated in the DNA collected from each patient using TaqMan(®) genotyping assays...
July 31, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28760986/pum1-is-a-biphasic-negative-regulator-of-innate-immunity-genes-by-suppressing-lgp2
#14
Yonghong Liu, Linlin Qu, Yuanyuan Liu, Bernard Roizman, Grace Guoying Zhou
PUM1 is an RNA binding protein shown to regulate the stability and function of mRNAs bearing a specific sequence. We report the following: (i) A key function of PUM1 is that of a repressor of key innate immunity genes by repressing the expression of LGP2. Thus, between 12 and 48 hours after transfection of human cells with siPUM1 RNA there was an initial (phase 1) upsurge of transcripts encoding LGP2, CXCL10, IL6, and PKR. This was followed 24 hours later (phase 2) by a significant accumulation of mRNAs encoding RIG-I, SP100, MDA5, IFIT1, PML, STING, and IFNβ...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760879/pact-facilitates-rna-induced-activation-of-mda5-by-promoting-mda5-oligomerization
#15
Pak-Yin Lui, Lok-Yin Roy Wong, Ting-Hin Ho, Shannon Wing Ngor Au, Chi-Ping Chan, Kin-Hang Kok, Dong-Yan Jin
MDA5 is a RIG-I-like cytoplasmic sensor of dsRNA and certain RNA viruses, such as encephalomyocarditis virus, for the initiation of the IFN signaling cascade in the innate antiviral response. The affinity of MDA5 toward dsRNA is low, and its activity becomes optimal in the presence of unknown cellular coactivators. In this article, we report an essential coactivator function of dsRNA-binding protein PACT in mediating the MDA5-dependent type I IFN response. Virus-induced and polyinosinic-polycytidylic acid-induced activation of MDA5 were severely impaired in PACT-knockout cells and attenuated in PACT-knockdown cells, but they were potentiated when PACT was overexpressed...
July 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28760668/rig-i-activation-protects-and-rescues-from-lethal-influenza-virus-infection-and-bacterial-superinfection
#16
Christoph Coch, Jan Phillip Stümpel, Vanessa Lilien-Waldau, Dirk Wohlleber, Beate M Kümmerer, Isabelle Bekeredjian-Ding, Georg Kochs, Natalio Garbi, Stephan Herberhold, Christine Schuberth-Wagner, Janos Ludwig, Winfried Barchet, Martin Schlee, Achim Hoerauf, Friedrich Bootz, Peter Staeheli, Gunther Hartmann, Evelyn Hartmann
Influenza A virus infection causes substantial morbidity and mortality in seasonal epidemic outbreaks, and more efficient treatments are urgently needed. Innate immune sensing of viral nucleic acids stimulates antiviral immunity, including cell-autonomous antiviral defense mechanisms that restrict viral replication. RNA oligonucleotide ligands that potently activate the cytoplasmic helicase retinoic-acid-inducible gene I (RIG-I) are promising candidates for the development of new antiviral therapies. Here, we demonstrate in an Mx1-expressing mouse model of influenza A virus infection that a single intravenous injection of low-dose RIG-I ligand 5'-triphosphate RNA (3pRNA) completely protected mice from a lethal challenge with influenza A virus for at least 7 days...
July 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28757363/poly-i-c-alleviates-obesity-related-pro-inflammatory-status-and-promotes-glucose-homeostasis
#17
Ying-Hui Wang, Yu-Gen Zhang
Obesity associated insulin resistance (IR) is implicated in chronic inflammation that mediated by the immune system. Imbalance between anti-inflammatory and pro-inflammatory response contributes to the origins and drivers of IR. However, cells of innate and adaptive immune system participate in the pathogenesis of IR, while glucose homeostasis related immune tolerance could be compromised high fat diet (HFD) reduced metabolic disorder. Although previous studies have demonstrated that anti-inflammatory therapy has a protective role in alleviating the pro-inflammatory status in HFD induced IR, the precise mechanism is still unclear...
July 27, 2017: Cytokine
https://www.readbyqxmd.com/read/28754636/molecular-cloning-characterization-and-expression-of-duck-2-5-oligoadenylate-synthetase-like-gene
#18
Ke-Ran Bi, Kai-Kai Han, Qing-Tao Liu, Dong-Min Zhao, Xin-Mei Huang, Yu-Zhuo Liu, Jing Yang, Yin Li
2'-5'-Oligoadenylate synthetase-like protein (OASL) is an interferon-inducible antiviral protein that exerts antiviral effects through the RNase L- or retinoic acid-inducible gene I (RIG-I)-dependent signalling pathway. In this study, we identified and cloned the OASL gene (named duOASL) from healthy adult Cherry Valley ducks. Full-length duOASL cDNA (1630bp) encoded a 504-amino acid polypeptide containing three conserved domains, namely, nucleotidyltransferase domain, 2'-5'-oligoadenylate synthetase domain, and two ubiquitin-like repeats...
July 25, 2017: Gene
https://www.readbyqxmd.com/read/28750037/generation-and-characterization-of-interferon-lambda-1-resistant-h1n1-influenza-a-viruses
#19
Natalia A Ilyushina, Vladimir Y Lugovtsev, Anastasia P Samsonova, Faruk G Sheikh, Nicolai V Bovin, Raymond P Donnelly
Influenza A viruses pose a constant potential threat to human health. In view of the innate antiviral activity of interferons (IFNs) and their potential use as anti-influenza agents, it is important to know whether viral resistance to these antiviral proteins can arise. To examine the likelihood of emergence of IFN-λ1-resistant H1N1 variants, we serially passaged the A/California/04/09 (H1N1) strain in a human lung epithelial cell line (Calu-3) in the presence of increasing concentrations of recombinant IFN-λ1 protein...
2017: PloS One
https://www.readbyqxmd.com/read/28745813/subversion-of-innate-immune-responses-by-francisella-involves-the-disruption-of-traf3-and-traf6-signaling-complexes
#20
Daniela Putzova, Swarupa Panda, Anetta Härtlova, Jiří Stulík, Nelson O Gekara
The success of pathogens depends on their ability to circumvent immune defenses. Francisella tularensis is one of the most infectious bacteria known. The remarkable virulence of Francisella is believed to be due to its capacity to evade or subvert the immune system, but how remains obscure. Here we show that Francisella triggers but concomitantly inhibits the Toll-like receptor (TLR), RIG-I-like receptor (RLR) and Cytoplasmic DNA (CDR) pathways. Francisella subverts these pathways at least in part by inhibiting K63-linked polyubiquitination and assembly of TRAF6 and TRAF3 complexes that control the transcriptional responses of PRRs...
July 26, 2017: Cellular Microbiology
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