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https://www.readbyqxmd.com/read/27899525/reactive-oxygen-species-induce-virus-independent-mavs-oligomerization-in-systemic-lupus-erythematosus
#1
Iwona A Buskiewicz, Theresa Montgomery, Elizabeth C Yasewicz, Sally A Huber, Michael P Murphy, Richard C Hartley, Ryan Kelly, Mary K Crow, Andras Perl, Ralph C Budd, Andreas Koenig
The increased expression of genes induced by type I interferon (IFN) is characteristic of viral infections and systemic lupus erythematosus (SLE). We showed that mitochondrial antiviral signaling (MAVS) protein, which normally forms a complex with retinoic acid gene I (RIG-I)-like helicases during viral infection, was activated by oxidative stress independently of RIG-I helicases. We found that chemically generated oxidative stress stimulated the formation of MAVS oligomers, which led to mitochondrial hyperpolarization and decreased adenosine triphosphate production and spare respiratory capacity, responses that were not observed in similarly treated cells lacking MAVS...
November 29, 2016: Science Signaling
https://www.readbyqxmd.com/read/27894672/mir-145-5p-regulates-the-rlr-signaling-pathway-in-miiuy-croaker-after-poly-i-c-stimulation-via-targeting-mda5
#2
Jingjing Han, Yuena Sun, Weihua Song, Tianjun Xu
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that participate in diverse biological processes via degrading the target mRNAs or repressing translation. In this study, the regulation of miRNA to the RLR (RIG-I-like receptor) signaling pathway by degrading the target mRNAs was researched in miiuy croaker. MDA5, a miR-145-5p putative target gene, was predicted by bioinformatics, and the target sites from the 3'untranslated region of MDA5 transcripts were confirmed using luciferase reporter assays. Pre-miR-145 was more effective in inhibiting MDA5 than miR-145-5p mimic, and the effect was dose- and time-dependent...
November 25, 2016: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/27881448/prion-like-polymerization-in-immunity-and-inflammation
#3
Xin Cai, Hui Xu, Zhijian J Chen
The innate immune system relies on receptors that sense common signs of infection to trigger a robust host-defense response. Receptors such as RIG-I and NLRP3 activate downstream adaptors mitochondrial antiviral signaling (MAVS) and apoptosis-associated speck-like protein (ASC), respectively, to propagate immune and inflammatory signaling. Recent studies have indicated that both MAVS and ASC form functional prion-like polymers to propagate immune signaling. Here, we summarize the biochemical, genetic, and structural studies that characterize the prion-like behavior of MAVS and ASC in their respective signaling pathways...
November 23, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27876623/identification-of-sea-perch-lateolabrax-japonicus-ribonucleoprotein-ptb-binding-1-involved-in-antiviral-immune-response-against-rgnnv
#4
Peng Jia, Wei Liu, Limin Chen, Yilin Jin, Jing Zhang, Kuntong Jia, Meisheng Yi
RIG-I-like receptors (RLRs) can recognize viral RNA and initiate innate antiviral response. In earlier studies, we demonstrated that RLRs were implicated in the antiviral immunity against RGNNV in the seawater fish sea perch (Lateolabrax japonicus). However, potential regulators of RLRs-mediated signaling pathways involved in RGNNV infection remain unclear. In this study, a novel ribonucleoprotein PTB-binding 1 (Raver1) of sea perch (LjRAVER1) was identified for the first time. The cDNA of LjRAVER1 was 4066 bp in length and encoded a deduced polypeptide of 733 amino acids...
November 20, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27866900/a-viral-deamidase-targets-the-helicase-domain-of-rig-i-to-block-rna-induced-activation
#5
Jun Zhao, Yi Zeng, Simin Xu, Jie Chen, Guobo Shen, Caiqun Yu, David Knipe, Weiming Yuan, Jian Peng, Wenqing Xu, Chao Zhang, Zanxian Xia, Pinghui Feng
RIG-I detects double-stranded RNA (dsRNA) to trigger antiviral cytokine production. Protein deamidation is emerging as a post-translational modification that chiefly regulates protein function. We report here that UL37 of herpes simplex virus 1 (HSV-1) is a protein deamidase that targets RIG-I to block RNA-induced activation. Mass spectrometry analysis identified two asparagine residues in the helicase 2i domain of RIG-I that were deamidated upon UL37 expression or HSV-1 infection. Deamidation rendered RIG-I unable to sense viral dsRNA, thus blocking its ability to trigger antiviral immune responses and restrict viral replication...
November 16, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27863906/post-translational-control-of-intracellular-pathogen-sensing-pathways
#6
REVIEW
Cindy Chiang, Michaela U Gack
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes...
November 15, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27853642/rig-i-activation-induces-the-release-of-extracellular-vesicles-with-antitumor-activity
#7
Juliane Daßler-Plenker, Katrin S Reiners, Jasper G van den Boorn, Hinrich P Hansen, Bastian Putschli, Sabine Barnert, Christine Schuberth-Wagner, Rolf Schubert, Thomas Tüting, Michael Hallek, Martin Schlee, Gunther Hartmann, Elke Pogge von Strandmann, Christoph Coch
Activation of the innate immune receptor retinoic acid-inducible gene I (RIG-I) by its specific ligand 5'-triphosphate-RNA (3pRNA) triggers antitumor immunity predominantly via NK cell activation and direct apoptosis induction in tumor cells. However, how NK cells are mobilized to attack the tumor cells remains elusive. Here, we show that RIG-I activation induced the secretion of extracellular vesicles (EVs) from melanoma cells, which by themselves revealed antitumor activity in vitro and in vivo. RIG-I-induced EVs from melanoma cells exhibited an increased expression of the NKp30-ligand (BAG6, BAT3) on their surface triggering NK cell-mediated lysis of melanoma cells via activation of the cytotoxicity NK cell-receptor NKp30...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27832807/sex-specific-variation-in-signaling-pathways-and-gene-expression-patterns-in-human-leukocytes-in-response-to-endotoxin-and-exercise
#8
Asghar Abbasi, Rodolfo de Paula Vieira, Felix Bischof, Michael Walter, Masoud Movassaghi, Nicole C Berchtold, Andreas M Niess, Carl W Cotman, Hinnak Northoff
BACKGROUND: While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. METHODS: We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study...
November 10, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27825367/involvement-of-the-different-lung-compartments-in-the-pathogenesis-of-ph1n1-influenza-virus-infection-in-ferrets
#9
Beatriz Vidaña, Jorge Martínez, Jaime Martorell, María Montoya, Lorena Córdoba, Mónica Pérez, Natàlia Majó
Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques...
November 8, 2016: Veterinary Research
https://www.readbyqxmd.com/read/27824940/invertebrate-iridescent-virus-6-a-dna-virus-stimulates-a-mammalian-innate-immune-response-through-rig-i-like-receptors
#10
Laura R H Ahlers, Reginaldo G Bastos, Aoi Hiroyasu, Alan G Goodman
Insects are not only major vectors of mammalian viruses, but are also host to insect-restricted viruses that can potentially be transmitted to mammals. While mammalian innate immune responses to arboviruses are well studied, less is known about how mammalian cells respond to viruses that are restricted to infect only invertebrates. Here we demonstrate that IIV-6, a DNA virus of the family Iridoviridae, is able to induce a type I interferon-dependent antiviral immune response in mammalian cells. Although IIV-6 is a DNA virus, we demonstrate that the immune response activated during IIV-6 infection is mediated by the RIG-I-like receptor (RLR) pathway, and not the canonical DNA sensing pathway via cGAS/STING...
2016: PloS One
https://www.readbyqxmd.com/read/27824081/the-nucleolar-protein-gltscr2-is-required-for-efficient-viral-replication
#11
Peng Wang, Wen Meng, Shi-Chong Han, Cui-Cui Li, Xiao-Jun Wang, Xiao-Jia Wang
Glioma tumor suppressor candidate region gene 2 protein (GLTSCR2) is a nucleolar protein. In the investigation of the role of GLTSCR2 that played in the cellular innate immune response to viral infection, we found GLTSCR2 supported viral replication of rhabdovirus, paramyxovirus, and coronavirus in cells. Viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm that enabled GLTSCR2 to attenuate type I interferon IFN-β and support viral replication. Cytoplasmic GLTSCR2 was able to interact with retinoic acid-inducible gene I (RIG-I) and the ubiquitin-specific protease 15 (USP15), and the triple interaction induced USP15 activity to remove K63-linked ubiquitination of RIG-I, leading to attenuation of RIG-I and IFN-β...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815826/rig-i-like-receptor-induced-irf3-mediated-pathway-of-apoptosis-ripa-a-new-antiviral-pathway
#12
REVIEW
Saurabh Chattopadhyay, Ganes C Sen
The innate immune response is the first line of host defense to eliminate viral infection. Pattern recognition receptors in the cytosol, such as RIG-I-like receptors (RLR) and Nod-like receptors (NLR), and membrane bound Toll like receptors (TLR) detect viral infection and initiate transcription of a cohort of antiviral genes, including interferon (IFN) and interferon stimulated genes (ISGs), which ultimately block viral replication. Another mechanism to reduce viral spread is through RIPA, the RLR-induced IRF3-mediated pathway of apoptosis, which causes infected cells to undergo premature death...
November 4, 2016: Protein & Cell
https://www.readbyqxmd.com/read/27807226/subcellular-localizations-of-rig-i-trim25-and-mavs-complexes
#13
M T Sánchez-Aparicio, J Ayllón, A Leo-Macias, T Wolff, A García-Sastre
: The RIG-I signaling pathway is essential for the recognition of viruses and the initiation of host IFN-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds MAVS, leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway, through the use of Bimolecular Fluorescence Complementation (BiFC) and super resolution microscopy. Dimers of RIG-I, TRIM25 and MAVS localize into different compartments...
November 2, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27788241/elevation-of-alanine-aminotransferase-activity-occurs-after-activation-of-the-cell-death-signaling-initiated-by-pattern-recognition-receptors-%C3%A2-but-before-activation-of-cytolytic-effectors-in-nk-or-cd8-t-cells-in-the-liver-during-acute-hcv-infection
#14
Youkyung H Choi, Nancy Jin, Fiona Kelly, SenthilKumar K Sakthivel, Tianwei Yu
Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles...
2016: PloS One
https://www.readbyqxmd.com/read/27769507/endogenous-retroelements-and-the-host-innate-immune-sensors
#15
X Mu, S Ahmad, S Hur
The ability to distinguish between self and nonself is the fundamental basis of the immune system in all organisms. The conceptual distinction between self and nonself, however, breaks down when it comes to endogenous retroviruses and other retroelements. While some retroelements retain the virus-like features including the capacity to replicate and reinvade the host genome, most have become inactive through mutations or host epigenetic silencing. And yet, accumulating evidence suggests that endogenous retroelements, both active and inactive, play important roles not only in pathogenesis of immune disorders, but also in proper functioning of the immune system...
2016: Advances in Immunology
https://www.readbyqxmd.com/read/27751656/molecular-requirements-for-sensing-of-intracellular-microbial-nucleic-acids-by-the-innate-immune-system
#16
Stefanie Luecke, Søren R Paludan
Nucleic acids sensors of the innate immune system recognize various RNA and DNA structures during infection to induce transcription of interferon and pro-inflammatory cytokines and activation of inflammasomes. Cytosolic RNA is recognized by RIG-I and MDA5, while intracellular DNA is sensed among others by cGAS, AIM2, IFI16 and RNA polymerase III. The diversity of nucleic acid species produced during infection in the cytosol and nucleus and the limited chemical differences between self and non-self nucleic acids challenge the host's innate pattern recognition system to ensure reliable sensing while avoiding immune activation by self nucleic acids...
October 14, 2016: Cytokine
https://www.readbyqxmd.com/read/27743998/zebrafish-stat6-negatively-regulates-ifn%C3%AF-1-production-by-attenuating-the-kinase-activity-of-tank-binding-kinase-1
#17
Shun Li, Long-Feng Lu, Scott E LaPatra, Dan-Dan Chen, Yong-An Zhang
The aquatic spring viremia of carp virus (SVCV) causes significant mortality in common carp (Cyprinus carpio), and TBK1 plays a crucial role in the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) system by phosphorylating its substrates to induce type I interferons (IFNs) and cellular antiviral responses. In this study, we report that zebrafish STAT6 is induced during SVCV infection and reduces IFNφ1 expression by suppressing TBK1 phosphorylation. A typical IFN stimulatory response element (ISRE) motif was found in the promoter region of zebrafish STAT6, and zebrafish STAT6 transcription was significantly upregulated in the early stages of virus infection...
February 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/27743889/the-tar-rna-binding-protein-is-required-for-immunoresponces-triggered-by-cardiovirus-infection
#18
Akihiko Komuro, Yuya Homma, Takaharu Negoro, Glen N Barber, Curt M Horvath
LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5...
October 12, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27718110/hiv-1-derived-single-stranded-rna-acts-as-activator-of-human-neutrophils
#19
Diana M Giraldo, Juan C Hernandez, Silvio Urcuqui-Inchima
Neutrophils are key effector cells of the innate immune system and are involved in the host defense against invading pathogens such as viruses. Recently, it was reported that HIV-1-neutrophil interaction triggers neutrophil activation and promotes expression of Toll-like receptors (TLRs). Here, we assessed the role of single-stranded RNA40 (ssRNA40) derived from HIV-1 in neutrophil activation. We observed functional activation of neutrophils in response to HIV-1-derived ssRNA40 based on the expression of TLR7/8, RIG-I, and MDA5, induction of cytokines (IL-6 and TNF-α), and the production of reactive oxygen species (ROS)...
October 7, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27708647/cherry-valley-ducks-mitochondrial-antiviral-signaling-protein-mediated-signaling-pathway-and-antiviral-activity-research
#20
Ning Li, Tianqi Hong, Rong Li, Yao Wang, Mengjiao Guo, Zongxi Cao, Yumei Cai, Sidang Liu, Tongjie Chai, Liangmeng Wei
Mitochondrial antiviral-signaling protein (MAVS), an adaptor protein of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated signal pathway, is involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS) was cloned from the spleen and analyzed. duMAVS was determined to have a caspase activation and recruitment domain at N-terminal, followed by a proline-rich domain and a transmembrane domain at C-terminal. Quantitative real-time PCR indicated that duMAVS was expressed in all tissues tested across a broad expression spectrum...
2016: Frontiers in Immunology
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