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https://www.readbyqxmd.com/read/28100675/protein-synthesis-inhibition-and-gadd34-control-ifn-%C3%AE-heterogeneous-expression-in-response-to%C3%A2-dsrna
#1
Alexandre Dalet, Rafael J Argüello, Alexis Combes, Lionel Spinelli, Sebastien Jaeger, Mathieu Fallet, Thien-Phong Vu Manh, Andreia Mendes, Jessica Perego, Marisa Reverendo, Voahirana Camosseto, Marc Dalod, Tobias Weil, Manuel A Santos, Evelina Gatti, Philippe Pierre
In innate immune responses, induction of type-I interferons (IFNs) prevents virus spreading while viral replication is delayed by protein synthesis inhibition. We asked how cells perform these apparently contradictory activities. Using single fibroblast monitoring by flow cytometry and mathematical modeling, we demonstrate that type-I IFN production is linked to cell's ability to enter dsRNA-activated PKR-dependent translational arrest and then overcome this inhibition by decreasing eIF2α phosphorylation through phosphatase 1c cofactor GADD34 (Ppp1r15a) expression...
January 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28099857/a-systems-approach-reveals-mavs-signaling-in-myeloid-cells-as-critical-for-resistance-to-ebola-virus-in-murine-models-of-infection
#2
Mukta Dutta, Shelly J Robertson, Atsushi Okumura, Dana P Scott, Jean Chang, Jeffrey M Weiss, Gail L Sturdevant, Friederike Feldmann, Elaine Haddock, Abhilash I Chiramel, Sanket S Ponia, Jonathan D Dougherty, Michael G Katze, Angela L Rasmussen, Sonja M Best
The unprecedented 2013-2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS), but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS(-/-) mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28094802/extrinsic-mavs-signaling-is-critical-for-treg-maintenance-of-foxp3-expression-following-acute-flavivirus-infection
#3
Andreia Da Costa, Esteban Garza, Jessica B Graham, Jessica L Swarts, Andrew G Soerens, Michael Gale, Jennifer M Lund
Given the rapid spread of flaviviruses such as West Nile virus (WNV) and Zika virus, it is critical that we develop a complete understanding of the key mediators of an effective anti-viral response. We previously demonstrated that WNV infection of mice deficient in mitochondrial antiviral-signaling protein (MAVS), the signaling adaptor for RNA helicases such as RIG-I, resulted in increased death and dysregulated immunity, which correlated with a failure of Treg expansion following infection. Thus, we sought to determine if intrinsic MAVS signaling is required for participation of Tregs in anti-WNV immunity...
January 17, 2017: Scientific Reports
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
#4
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/28073693/crosstalk-between-cytoplasmic-rig-i-and-sting-sensing-pathways
#5
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/28053109/matrix-metalloproteinase-activity-in-infections-by-an-encephalitic-virus-mouse-adenovirus-type-1
#6
Shanna L Ashley, Carla D Pretto, Matthew T Stier, Padma Kadiyala, Luiza Castro-Jorge, Tien-Huei Hsu, Robert Doherty, Kelly E Carnahan, Maria G Castro, Pedro R Lowenstein, Katherine R Spindler
: Mouse adenovirus type 1 (MAV-1) infection causes encephalitis in susceptible strains of mice and alters the permeability of infected brains to small molecules, which indicates disruption of the blood-brain barrier (BBB). In pathologic conditions, matrix metalloproteinases (MMPs) can disrupt the BBB through their proteolytic activity on basement membrane and tight junction proteins. We examined whether MAV-1 infection alters MMP activity in vivo and in vitro. Infected MAV-1-susceptible SJL mice had higher MMP2 and MMP9 activity in brains, measured by gelatin zymography, than mock infected mice...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28049762/the-tyrosine-kinase-src-promotes-phosphorylation-of-the-kinase-tbk1-to-facilitate-type-i-interferon-production-after-viral-infection
#7
Xuelian Li, Mingjin Yang, Zhou Yu, Songqing Tang, Lei Wang, Xuetao Cao, Taoyong Chen
Various pattern recognition receptors (PRRs) are activated in response to viral infection to stimulate the production of type I interferons (IFNs). However, central to the responses of all of these receptors is their activation of the kinase TBK1, which stimulates transcription by IFN regulatory factor 3 (IRF3). We investigated the mechanism by which the kinase activity of TBK1 is stimulated in response to viral infection. We found that the tyrosine kinase Src promoted the phosphorylation of TBK1 on Tyr(179) upon viral infection of RAW264...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28046700/mo-de-207b-11-reliability-of-pet-ct-radiomics-features-in-functional-and-morphological-components-of-nsclc-lesions-a-repeatability-analysis-in-a-prospective-multicenter-cohort
#8
M Desseroit, F Tixier, M Majdoub, W Weber, B Siegel, C Cheze Le Rest, D Visvikis, M Hatt
PURPOSE: The goal of this study was to evaluate the repeatability of radiomics features (intensity, shape and heterogeneity) in both PET and low-dose CT components of test-retest FDG-PET/CT images in a prospective multicenter cohort of 74 NSCLC patients from ACRIN 6678 and a similar Merck trial. METHODS: Seventy-four patients with stage III-IV NCSLC were prospectively included. The primary tumor and up to 3 additional lesions per patient were analyzed. The Fuzzy Locally Adaptive Bayesian algorithm was used to automatically delineate metabolically active volume (MAV) in PET...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28025524/a-multi-sensor-fusion-mav-state-estimation-from-long-range-stereo-imu-gps-and-barometric-sensors
#9
Yu Song, Stephen Nuske, Sebastian Scherer
State estimation is the most critical capability for MAV (Micro-Aerial Vehicle) localization, autonomous obstacle avoidance, robust flight control and 3D environmental mapping. There are three main challenges for MAV state estimation: (1) it can deal with aggressive 6 DOF (Degree Of Freedom) motion; (2) it should be robust to intermittent GPS (Global Positioning System) (even GPS-denied) situations; (3) it should work well both for low- and high-altitude flight. In this paper, we present a state estimation technique by fusing long-range stereo visual odometry, GPS, barometric and IMU (Inertial Measurement Unit) measurements...
December 22, 2016: Sensors
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#10
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28011935/ttll12-inhibits-the-activation-of-cellular-antiviral-signaling-through-interaction-with-visa-mavs
#11
Lin-Gao Ju, Yuan Zhu, Pin-Ji Lei, Dong Yan, Kun Zhu, Xiang Wang, Qing-Lan Li, Xue-Jing Li, Jian-Wen Chen, Lian-Yun Li, Min Wu
Upon virus infection, host cells use retinoic-acid-inducible geneI I (RIG-I)-like receptors to recognize viral RNA and activate type I IFN expression. To investigate the role of protein methylation in the antiviral signaling pathway, we screened all the SET domain-containing proteins and identified TTLL12 as a negative regulator of RIG-I signaling. TTLL12 contains SET and TTL domains, which are predicted to have lysine methyltransferase and tubulin tyrosine ligase activities, respectively. Exogenous expression of TTLL12 represses IFN-β expression induced by Sendai virus...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27997564/nonstructural-protein-11-of-porcine-reproductive-and-respiratory-syndrome-virus-suppresses-both-mavs-and-rig-i-expression-as-one-of-the-mechanisms-to-antagonize-type-i-interferon-production
#12
Yan Sun, Hanzhong Ke, Mingyuan Han, Ning Chen, Weihuan Fang, Dongwan Yoo
Type I interferons (IFN-α/β) play a key role in antiviral defense, and porcine reproductive and respiratory syndrome virus (PRRSV) is known to down-regulate the IFN response in virus-infected cells and pigs. In this study, we showed that the overexpression of nsp11 of PRRSV induced a strong suppression of IFN production. Nsp11 suppressed both IRF3 and NF-κB activities when stimulated with a dsRNA analogue and TNF-α, respectively. This suppression was RLR dependent, since the transcripts and proteins of MAVS and RIG-I, two critical factors in RLR-mediated pathway, were both found to be reduced in the presence of overexpressed nsp11...
2016: PloS One
https://www.readbyqxmd.com/read/27995135/trim25-identification-in-the-chinese-goose-gene-structure-tissue-expression-profiles-and-antiviral-immune-responses-in-vivo-and-in-vitro
#13
Yunan Wei, Hao Zhou, Anqi Wang, Lipei Sun, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Kunfeng Sun, Xiaoyue Chen, Anchun Cheng, Shun Chen
The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein play a critical role in the interferon (IFN) response during RNA virus infection. The tripartite motif containing 25 proteins (TRIM25) was reported to modify caspase activation and RIG-I recruitment domains (CARDs) via ubiquitin. These modifications allow TRIM25 to interact with mitochondrial antiviral signaling molecules (MAVs) and form CARD-CARD tetramers. Goose TRIM25 was cloned from gosling lungs, which possess a 1662 bp open reading flame (ORF)...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27992402/the-ubiquitin-e3-ligase-trim31-promotes-aggregation-and-activation-of-the-signaling-adaptor-mavs-through-lys63-linked-polyubiquitination
#14
Bingyu Liu, Meng Zhang, Honglei Chu, Honghai Zhang, Haifeng Wu, Guanhua Song, Peng Wang, Kai Zhao, Jinxiu Hou, Xueer Wang, Lei Zhang, Chengjiang Gao
The signaling adaptor MAVS forms prion-like aggregates to activate an innate antiviral immune response after viral infection. However, the molecular mechanisms that regulate MAVS aggregation are poorly understood. Here we identified TRIM31, an E3 ubiquitin ligase of the TRIM family of proteins, as a regulator of MAVS aggregation. TRIM31 was recruited to mitochondria after viral infection and specifically regulated antiviral signaling mediated by RLR pattern-recognition receptors. TRIM31-deficient mice were more susceptible to infection with RNA virus than were wild-type mice...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27980081/ddx3-directly-regulates-traf3-ubiquitination-and-acts-as-a-scaffold-to-coordinate-assembly-of-signalling-complexes-downstream-of-mavs
#15
Lili Gu, Anthony Fullam, Niamh McCormack, Yvette Hoehn, Martina Schroeder
Human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IκB-kinase-ε (IKKε), the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination...
December 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27956705/arfgap-domain-containing-protein-2-adap2-integrates-upstream-and-downstream-modules-of-rig-i-signaling-and-facilitates-type-i-interferon-production
#16
Pradeep Bist, Soo Yeon Kim, Niyas Kudukil Pulloor, Kathleen McCaffrey, Sajith Kumar Nair, Yiliu Liu, Rongtuan Lin, Manoj N Krishnan
: Transcription of Type I interferon during RNA virus infection requires signal communication between several Pattern recognition receptor (PRR)-adaptor complexes located at distinct subcellular membranous compartments and a central cytoplasmic TBK1-IRF3 kinase-transcription factor module. However, how cell integrates signal transduction through spatially distinct modules of antiviral signaling pathways is less defined. RIG-I is a major cytosolic PRR involved in the control of several RNA viruses...
December 12, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27923925/biliary-secretion-of-quasi-enveloped-human-hepatitis-a-virus
#17
Asuka Hirai-Yuki, Lucinda Hensley, Jason K Whitmire, Stanley M Lemon
: Hepatitis A virus (HAV) is an unusual picornavirus that is released from cells cloaked in host-derived membranes. These quasi-enveloped virions (eHAV) are the only particle type circulating in blood during infection, whereas only nonenveloped virions are shed in feces. The reason for this is uncertain. Hepatocytes, the only cell type known to support HAV replication in vivo, are highly polarized epithelial cells with basolateral membranes facing onto hepatic (blood) sinusoids and apical membranes abutting biliary canaliculi from which bile is secreted to the gut...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27903802/a-protective-role-for-il-1-signaling-during-mouse-adenovirus-type-1-induced-encephalitis
#18
Luiza A Castro-Jorge, Carla Pretto, Asa Smith, Oded Foreman, Kelly E Carnahan, Katherine R Spindler
: IL-1β, an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor, Il1r1(-/-) Il1r1(-/-) mice had lower survival, higher disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokines and chemokines than control C57BL/6 mice. We also examined infections of mice defective in IL-1β production (Pycard(-/-)mice) and mice defective in trafficking of TLRs to the endosome (Unc93b1(-/-) mice)...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903800/genetic-variability-of-myxoma-virus-genomes
#19
Christoph Braun, Andrea Thürmer, Rolf Daniel, Anne-Kathrin Schultz, Ingo Bulla, Horst Schirrmeier, Dietmar Mayer, Andreas Neubert, Claus-Peter Czerny
: Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 Myxoma virus strains (MYXV) were sequenced: German field isolates Munich-1, FLI-H, 2604, 3207, vaccine strain MAV, and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207) in size...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27899525/reactive-oxygen-species-induce-virus-independent-mavs-oligomerization-in-systemic-lupus-erythematosus
#20
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
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