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https://www.readbyqxmd.com/read/28109007/retinoic-acid-inducible-gene-i-rig-i-like-receptors-rlrs-in-fish-current-knowledge-and-future-perspectives
#1
REVIEW
Shan Nan Chen, Peng Fei Zou, Pin Nie
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2 together with the downstream molecules such as MITA, TRAF3 and TBK1 have been identified in a range of fish species. However, it is a bit unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic double-stranded RNA (dsRNA), poly(I:C), leading to the production of type I IFNs and the expression of IFN stimulated genes (ISGs)...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28100701/self-cytoplasmic-dna-upregulates-the-mutator-enzyme-apobec3a-leading-to-chromosomal-dna-damage
#2
Rodolphe Suspène, Bianka Mussil, Hélène Laude, Vincent Caval, Noémie Berry, Mohamed S Bouzidi, Valérie Thiers, Simon Wain-Hobson, Jean-Pierre Vartanian
Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal...
January 18, 2017: Nucleic Acids Research
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
#3
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
#4
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/28090671/lgp2-plays-an-essential-role-in-hcv-infection-induced-interferon-responses
#5
Lei Hei, Jin Zhong
: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are cytosolic pattern recognition receptors (PRR) that detect non-self RNA and activate downstream interferon (IFN) signaling. One of the RLRs, Laboratory of genetics and physiology 2 (LGP2) was originally thought to be a negative feedback regulator in RIG-I signaling pathway, but growing evidence indicates LGP2 is one co-factor of Melanoma Differentiation-Associated protein 5 (MDA5) in MDA5-mediated IFN signaling activation...
January 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28087918/-research-progress-on-the-role-of-tank-binding-kinase-1-in-anti-virus-innate-immune-response
#6
Xue Wang, Yuchuan Zhang, Wei Chen
The innate immune response against viral infection is mainly relies on type I interferon, the production of which is mediated by TANK-binding kinase 1 (TBK1). It is revealed that the downstream TBK1 is activated by viral nucleic acid sensors RIG-I, cGAS and TLR3. The activity of TBK1 is complexly and precisely regulated by different type of protein modifications, including phosphorylation, ubiquitination and Sumolylation. This article focuses on the role of TBK1 in anti-viral innate immunity and the regulatory mechanism for the TBK1 activation...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
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
#7
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/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/28077601/a-new-rna-based-adjuvant-enhances-virus-specific-vaccine-responses-by-locally-triggering-tlr-and-rlh-dependent-effects
#9
Annett Ziegler, Claudia Soldner, Stefan Lienenklaus, Julia Spanier, Stephanie Trittel, Peggy Riese, Thomas Kramps, Siegfried Weiss, Regina Heidenreich, Edith Jasny, Carlos A Guzmán, Karl-Josef Kallen, Mariola Fotin-Mleczek, Ulrich Kalinke
Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Furthermore, such sera neutralized influenza virus, whereas this effect was not detected upon vaccination with the subunit vaccine alone...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28073693/crosstalk-between-cytoplasmic-rig-i-and-sting-sensing-pathways
#10
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/28063015/innate-immunity-against-legionella-pneumophila-during-pulmonary-infections-in-mice
#11
REVIEW
Bonggoo Park, Gayoung Park, Jiyoung Kim, Seon Ah Lim, Kyung-Mi Lee
Legionella pneumophila is an etiological agent of the severe pneumonia known as Legionnaires' disease (LD). This gram-negative bacterium is thought to replicate naturally in various freshwater amoebae, but also replicates in human alveolar macrophages. Inside host cells, legionella induce the production of non-endosomal replicative phagosomes by injecting effector proteins into the cytosol. Innate immune responses are first line defenses against legionella during early phases of infection, and distinguish between legionella and host cells using germline-encoded pattern recognition receptors such as Toll-like receptors , NOD-like receptors, and RIG-I-like receptors, which sense pathogen-associated molecular patterns that are absent in host cells...
January 6, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28060562/pathogen-recognition-and-toll-like-receptor-targeted-therapeutics-in-innate-immune-cells
#12
Sarang Tartey, Osamu Takeuchi
The innate immune system deploys a variety of pattern-recognition receptors (PRRs) which include Toll-like receptors (TLRs), RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors to detect the invasion of pathogens and initiate protective responses. The intercellular and intracellular orchestration of signals from different PRRs, their endogenous or microbial ligands and accessory molecules determine the stimulatory or inhibitory responses. Progressing over the last two decades, considerable research on the molecular mechanisms underlying host-pathogen interactions has led to a paradigm shift of our understanding of TLR signaling in the innate immune system...
January 6, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28060376/induction-of-necroptotic-cell-death-by-viral-activation-of-the-rig-i-or-sting-pathway
#13
Suruchi N Schock, Neha V Chandra, Yuefang Sun, Takashi Irie, Yoshinori Kitagawa, Bin Gotoh, Laurent Coscoy, Astar Winoto
Necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase RIP1 and its family member RIP3. Necroptosis occurs when RIP1 is deubiquitinated to form a complex with RIP3 in cells deficient in the death receptor adapter molecule FADD or caspase-8. Necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. To see how general the interplay between viruses and necroptosis is, we surveyed seven different viruses...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28057020/rna-virus-receptor-rig-i-monitors-gut-microbiota-and-inhibits-colitis-associated-colorectal-cancer
#14
Houbao Zhu, Wang-Yang Xu, Zhiqiang Hu, Hongxin Zhang, Yan Shen, Shunyuan Lu, Chaochun Wei, Zhu-Gang Wang
BACKGROUND: Retinoic acid-inducible gene-I (Rig-I) is an intracellular viral RNA receptor, which specifically recognizes double-stranded viral RNA initiating antiviral innate immunity. Increasing evidences showed that Rig-I had broader roles in antibacterial immunity and cancer protection. However, the potential roles and mechanisms of Rig-I in gut flora regulation and colorectal cancer (CRC) progression remain unclear. METHODS: Immunohistochemistry was performed to detect Rig-I protein in 38 pairs of CRC tissue and matched adjacent mucosa, and immunofluorescence and western blot were also used to detect Rig-I protein expression in AOM/DSS-induced mice CRC samples...
January 5, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28056062/antiviral-efficacy-and-host-immune-response-induction-during-sequential-treatment-with-sb-9200-followed-by-entecavir-in-woodchucks
#15
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
https://www.readbyqxmd.com/read/28042704/development-of-an-in-vitro-immunobiotic-evaluation-system-against-rotavirus-infection-in-bovine-intestinal-epitheliocytes
#16
H Kobayashi, P Kanmani, T Ishizuka, A Miyazaki, J Soma, L Albarracin, Y Suda, T Nochi, H Aso, N Iwabuchi, J-Z Xiao, T Saito, J Villena, H Kitazawa
The bovine intestinal epithelial cell line (BIE cells) expresses the Toll-like receptor (TLR)3 and is able to mount an antiviral immune response after the stimulation with poly(I:C). In the present study, we aimed to further characterise the antiviral defence mechanisms in BIE cells by evaluating the innate immune response triggered by rotavirus (RV) infection. In addition, we attempted to determine whether immunobiotic bifidobacteria are able to confer protection of BIE cells against RV infection by beneficially modulating the antiviral immune response...
January 2, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28041664/early-gene-activation-initiates-neuroinflammation-prior-to-vsv-neuroinvasion-impact-on-antiviral-responses-and-sleep
#17
Richard P Ciavarra, Patric Lundberg, Mayumi Machida, Marta A Ambrozewicz, Laurie L Wellman, Kimberly Breving, Christina Steel, Larry D Sanford
Rapid eye movement (REM) sleep is rapidly and persistently suppressed during vesicular stomatitis virus (VSV) encephalitis in C57Bl/6J (B6) mice. REM sleep suppression was associated with a complex global brain chemokine/cytokine response with bimodal kinetics although regionally distinct cytokine profiles were readily identified. Cytokine mRNA was translated either immediately or suppressed until the pathogen was cleared from the CNS. Innate signaling pathway (TLRs, RIG-I) activation occurred rapidly and sequentially prior to VSV neuroinvasion suggesting that antiviral states are quickly established in the CNS in advance of viral pathogen penetration...
December 29, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28031478/trim65-catalized-ubiquitination-is-essential-for-mda5-mediated-antiviral-innate-immunity
#18
Xueting Lang, Tiantian Tang, Tengchuan Jin, Chen Ding, Rongbin Zhou, Wei Jiang
MDA5 plays a critical role in antiviral innate immunity by functioning as a cytoplasmic double-stranded RNA sensor that can activate type I interferon signaling pathways, but the mechanism for the activation of MDA5 is poorly understood. Here, we show that TRIM65 specifically interacts with MDA5 and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. Trim65 deficiency abolishes MDA5 agonist or encephalomyocarditis virus (EMCV)-induced interferon regulatory factor 3 (IRF3) activation and type I interferon production but has no effect on retinoic acid-inducible I (RIG-I), Toll-like receptor 3 (TLR3), or cyclic GMP-AMP synthase signaling pathways...
December 28, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28011935/ttll12-inhibits-the-activation-of-cellular-antiviral-signaling-through-interaction-with-visa-mavs
#19
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
#20
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
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