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https://www.readbyqxmd.com/read/28325765/caenorhabditis-elegans-rig-i-homolog-mediates-antiviral-rna-interference-downstream-of-dicer-dependent-biogenesis-of-viral-small-interfering-rnas
#1
Stephanie R Coffman, Jinfeng Lu, Xunyang Guo, Jing Zhong, Hongshan Jiang, Gina Broitman-Maduro, Wan-Xiang Li, Rui Lu, Morris Maduro, Shou-Wei Ding
Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA interference (RNAi) pathways in plants, insects, nematodes, and mammals. Antiviral RNAi in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), not found in plants and insects but highly homologous to mammalian retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral RNA sensors that trigger innate immunity against RNA virus infection...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28318042/beyond-sensing-rig-i-continues-to-expand-its-antiviral-effector-functions
#2
EDITORIAL
Amy El Stone, Michael Gale
No abstract text is available yet for this article.
March 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28303593/sb-9200-a-novel-agonist-of-innate-immunity-shows-potent-antiviral-activity-against-resistant-hcv-variants
#3
Meleri Jones, Morven E Cunningham, Peter Wing, Sampath DeSilva, Rupa Challa, Anjaneyulu Sheri, Seetharamaiyer Padmanabhan, Radhakrishnan P Iyer, Brent E Korba, Nezam Afdhal, Graham R Foster
SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log10 . Here, we demonstrate the antiviral activity of SB 9200 against a HCV replicon system and patient derived virus...
March 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28298903/apoptosis-toll-like-rig-i-like-and-nod-like-receptors-are-pathways-jointly-induced-by-diverse-respiratory-bacterial-and-viral-pathogens
#4
Isidoro Martínez, Juan C Oliveros, Isabel Cuesta, Jorge de la Barrera, Vicente Ausina, Cristina Casals, Alba de Lorenzo, Ernesto García, Belén García-Fojeda, Junkal Garmendia, Mar González-Nicolau, Alicia Lacoma, Margarita Menéndez, David Moranta, Amelia Nieto, Juan Ortín, Alicia Pérez-González, Cristina Prat, Elisa Ramos-Sevillano, Verónica Regueiro, Ariel Rodriguez-Frandsen, Dolores Solís, José Yuste, José A Bengoechea, José A Melero
Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28295214/negative-regulators-of-the-rig-i-like-receptor-signaling-pathway
#5
REVIEW
Kendra M Quicke, Michael S Diamond, Mehul S Suthar
Upon recognition of specific molecular patterns on microbes, host cells trigger an innate immune response, which culminates in the production of type I interferons (IFNs), pro-inflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of this response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection, whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295207/human-gestation-associated-tissues-express-functional-cytosolic-nucleic-acid-sensing-pattern-recognition-receptors
#6
Aled H Bryant, Georgina E Menzies, Louis M Scott, Samantha Spencer-Harty, Lleucu B Davies, Rachel A Smith, Ruth H Jones, Catherine A Thornton
The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways that yield a cytokine output in response to pathogenic stimuli have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR3, 7, 8 and 9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors (RIG-I, MDA5 and LGP2) in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model...
March 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28287082/e3-ligase-fbxw7-is-critical-for-rig-i-stabilization-during-antiviral-responses
#7
Yinjing Song, Lihua Lai, Zhenlu Chong, Jia He, Yuanyuan Zhang, Yue Xue, Yiwei Xie, Songchang Chen, Ping Dong, Luoquan Chen, Zhimin Chen, Feng Dai, Xiaopeng Wan, Peng Xiao, Xuetao Cao, Yang Liu, Qingqing Wang
Viruses can escape from host recognition by degradation of RIG-I or interference with the RIG-I signalling to establish persistent infections. However, the mechanisms by which host cells stabilize RIG-I protein for avoiding its degradation are largely unknown. We report here that, upon virus infection, the E3 ubiquitin ligase FBXW7 translocates from the nucleus into the cytoplasm and stabilizes RIG-I. FBXW7 interacts with SHP2 and mediates the degradation and ubiquitination of SHP2, thus disrupting the SHP2/c-Cbl complex, which mediates RIG-I degradation...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28286505/mda5-induces-a-stronger-interferon-response-than-rig-i-to-gcrv-infection-through-a-mechanism-involving-the-phosphorylation-and-dimerization-of-irf3-and-irf7-in-cik-cells
#8
Quanyuan Wan, Chunrong Yang, Youliang Rao, Zhiwei Liao, Jianguo Su
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are critical cytosolic sensors that trigger the production of interferons (IFNs). Though their recognition functions are well identified, their unique roles in the downstream signal transduction remain to be elucidated. Herein, we report the differential effect between grass carp (Ctenopharyngodon idella) MDA5 (CiMDA5) and CiRIG-I on the production of various IFNs upon grass carp reovirus (GCRV) infection in C. idella kidney (CIK) cell line...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28281905/implications-of-toll-like-receptors-in-ebola-infection
#9
Amene Saghazadeh, Nima Rezaei
The potential roles of toll-like receptors (TLRs) in immunopathogenesis of Ebola virus disease should be unraveled to provoke possible prophylactic or therapeutic implications of TLRs for EVD. Areas covered: The Ebola virus (EBOV) infection virtually paralyses all the main mechanisms responsible for induction of type I interferon (IFN-I) response. To summarize, EBOV infection interferes with: a) the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway that is mediated by TLR3 and TLR4 signaling; b) the interferon regulatory factor 7 (IRF7) pathway that is stimulated by TLR7 and TLR9; c) the intracellular signaling that is induced by retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs); and d) the autocrine/paracrine feedback loop that is mediated by the IFN-stimulated gene factor 3 (ISGF3) complex...
April 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28279563/a-small-molecule-irf3-agonist-functions-as-an-influenza-vaccine-adjuvant-by-modulating-the-antiviral-immune-response
#10
Peter Probst, John B Grigg, Myra Wang, Ernesto Muñoz, Yueh-Ming Loo, Renee C Ireton, Michael Gale, Shawn P Iadonato, Kristin M Bedard
Vaccine adjuvants are essential to drive a protective immune response in cases where vaccine antigens are weakly immunogenic, where vaccine antigen is limited, or where an increase in potency is needed for a specific population, such as the elderly. To discover novel vaccine adjuvants, we used a high-throughput screen (HTS) designed to identify small-molecule agonists of the RIG-I-like receptor (RLR) pathway leading to interferon regulatory factor 3 (IRF3) activation. RLRs are a group of cytosolic pattern-recognition receptors that are essential for the recognition of viral nucleic acids during infection...
March 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28276468/nv-proteins-of-fish-novirhabdovirus-recruit-cellular-ppm1bb-protein-phosphatase-and-antagonize-rig-i-mediated-ifn-induction
#11
Stéphane Biacchesi, Emilie Mérour, Didier Chevret, Annie Lamoureux, Julie Bernard, Michel Brémont
Non virion (NV) protein expression is critical for fish Novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV), in vivo pathogenesis. However, the mechanism by which NV promotes the viral replication is still unclear. We developed an approach based on reverse genetics and interactomic and identified several NV-associated cellular partners underlying cellular pathways as potential viral targets. Among these cell partners, we showed that NV proteins specifically interact with a protein phosphatase, Mg(2+)/Mn(2+)-dependent, 1Bb (PPM1Bb) and recruit it in the close vicinity of mitochondria, a subcellular compartment important for retinoic acid-inducible gene-I- (RIG-I)-mediated interferon induction pathway...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273895/the-dynamic-interacting-landscape-of-mapl-reveals-essential-functions-for-sumoylation-in-innate-immunity
#12
Karine Doiron, Vanessa Goyon, Etienne Coyaud, Sanjeeva Rajapakse, Brian Raught, Heidi M McBride
Activation of the innate immune response triggered by dsRNA viruses occurs through the assembly of the Mitochondrial Anti-Viral Signaling (MAVS) complex. Upon recognition of viral dsRNA, the cytosolic receptor RIG-I is activated and recruited to MAVS to activate the immune signaling response. We here demonstrate a strict requirement for a mitochondrial anchored protein ligase, MAPL (also called MUL1) in the signaling events that drive the transcriptional activation of antiviral genes downstream of Sendai virus infection, both in vivo and in vitro...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273165/transcriptome-profiling-of-influenza-a-virus-infected-lung-epithelial-a549-cells-with-lariciresinol-4-%C3%AE-d-glucopyranoside-treatment
#13
Beixian Zhou, Jing Li, Xiaoli Liang, Zifeng Yang, Zhihong Jiang
The influenza A virus is an acute contagious pathogen that affects the human respiratory system and can cause severe lung disease and even death. Lariciresinol-4-β-D-glucopyranoside is a lignan that is extracted from Isatis indigotica, which is a medicinal herb plant that was commonly applied to treat infections, the common cold, fever and inflammatory diseases. Our previous study demonstrated that lariciresinol-4-β-D-glucopyranoside possesses anti-viral and anti-inflammatory properties. However, the comprehensive and detailed mechanisms that underlie the effect of lariciresinol-4-β-D-glucopyranoside interventions against influenza virus infection remain to be elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28267631/transcriptome-analysis-of-ruditapes-philippinarum-hepatopancreas-provides-insights-into-immune-signaling-pathways-under-vibrio-anguillarum-infection
#14
Yipeng Ren, Junli Xue, Huanhuan Yang, Baoping Pan, Wenjun Bu
The Manila clam, Ruditapes philippinarum, is one of the most economically important aquatic clams that are harvested on a large scale by the mariculture industry in China. However, increasing reports of bacterial pathogenic diseases have had a negative effect on the aquaculture industry of R. philippinarum. In the present study, the two transcriptome libraries of untreated (termed H) and challenged Vibrio anguillarum (termed HV) hepatopancreas were constructed and sequenced from Manila clam using an Illumina-based paired-end sequencing platform...
March 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28250263/lambda-interferons-inhibit-herpes-simplex-virus-type-2-replication-in-human-cervical-epithelial-cells-through-activation-of-jak-stat-pathway
#15
Zhu Li, Xuan Lu, Yufan Zhu, Pengfei Cheng, Shi Liu, Yi Zhang, Jingfeng Tang, Sijun Yang, Li Zhou
Herpes Simplex Virus Type 2 (HSV-2) is associated with a variety of diseases, resulting in world-wide health problems. Our early study showed that lambda-interferons (IFN-λs) induced by activation of the toll-like receptors 3/ retinoic acid-inducible protein I (TLR3/RIG-I) signaling pathways contribute to inhibition of HSV-2 replication in the human cervical epithelial cells. However, anti-HSV-2 mechanisms and specific differences in signaling transduction by different IFN-λs in human cervical epithelial cells are unclear...
February 28, 2017: Japanese Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28250012/innate-immunity-to-rna-virus-is-regulated-by-temporal-and-reversible-sumoylation-of-rig-i-and-mda5
#16
Ming-Ming Hu, Chen-Yang Liao, Qing Yang, Xue-Qin Xie, Hong-Bing Shu
Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. How RIG-I and MDA5 are dynamically regulated in innate antiviral response is not well understood. Here, we show that TRIM38 positively regulates MDA5- and RIG-I-mediated induction of downstream genes and acts as a SUMO E3 ligase for their dynamic sumoylation at K43/K865 and K96/K888, respectively, before and after viral infection. The sumoylation of MDA5 and RIG-I suppresses their K48-linked polyubiquitination and degradation in uninfected or early-infected cells...
March 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28248290/systems-based-analysis-of-rig-i-dependent-signalling-identifies-khsrp-as-an-inhibitor-of-rig-i-receptor-activation
#17
Stephen Soonthornvacharin, Ariel Rodriguez-Frandsen, Yingyao Zhou, Felipe Galvez, Nicholas J Huffmaster, Shashank Tripathi, Vinod R M T Balasubramaniam, Atsushi Inoue, Elisa de Castro, Hong Moulton, David A Stein, María Teresa Sánchez-Aparicio, Paul D De Jesus, Quy Nguyen, Renate König, Nevan J Krogan, Adolfo García-Sastre, Sunnie M Yoh, Sumit K Chanda
Retinoic acid-inducible gene I (RIG-I) receptor recognizes 5'-triphosphorylated RNA and triggers a signalling cascade that results in the induction of type-I interferon (IFN)-dependent responses. Its precise regulation represents a pivotal balance between antiviral defences and autoimmunity. To elucidate the cellular cofactors that regulate RIG-I signalling, we performed two global RNA interference analyses to identify both positive and negative regulatory nodes operating on the signalling pathway during virus infection...
March 1, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#18
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28222782/identification-of-mirna-mrna-crosstalk-in-cd4-t-cells-during-hiv-1-infection-by-integrating-transcriptome-analyses
#19
Qibin Liao, Jin Wang, Zenglin Pei, Jianqing Xu, Xiaoyan Zhang
BACKGROUND: HIV-1-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7-10 years, but keeping high CD4(+) T cell counts and low viral load in the absence of antiretroviral treatment, while loss of CD4(+) T cells and high viral load were observed in the most of HIV-1-infected individuals with chronic progressors (CPs) However, the mechanisms of different clinical outcomes in HIV-1 infection needs to be further resolved. METHODS: To identify microRNAs (miRNAs) and their target genes related to distinct clinical outcomes in HIV-1 infection, we performed the integrative transcriptome analyses in two series GSE24022 and GSE6740 by GEO2R, R, TargetScan, miRDB, and Cytoscape softwares...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28216575/promising-targets-for-cancer-immunotherapy-tlrs-rlrs-and-sting-mediated-innate-immune-pathways
#20
REVIEW
Kai Li, Shuai Qu, Xi Chen, Qiong Wu, Ming Shi
Malignant cancers employ diverse and intricate immune evasion strategies, which lead to inadequately effective responses of many clinical cancer therapies. However, emerging data suggest that activation of the tolerant innate immune system in cancer patients is able, at least partially, to counteract tumor-induced immunosuppression, which indicates triggering of the innate immune response as a novel immunotherapeutic strategy may result in improved therapeutic outcomes for cancer patients. The promising innate immune targets include Toll-like Receptors (TLRs), RIG-I-like Receptors (RLRs), and Stimulator of Interferon Genes (STING)...
February 14, 2017: International Journal of Molecular Sciences
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