The Experts below are selected from a list of 26776770 Experts worldwide ranked by ideXlab platform
Weilin Chen - One of the best experts on this subject based on the ideXlab platform.
-
usp14 promotes k63 linked rig i deubiquitination and suppresses antiviral immune responses
European Journal of Immunology, 2019Co-Authors: Hongrui Li, Zizhao Zhao, Xibao Zhao, Juan Yu, Jing Ling, Jianzhong Shen, Weilin ChenAbstract:: Retinoic acid-inducible gene I (RIG-I) is a critical RNA virus sensor that initiates antiviral immune response through K63-linked ubiquitination. In this study, we demonstrated USP14, a deubiquitinating enzyme, as a negative regulator in antiviral responses by directly deubiquitinating K63-linked RIG-I. USP14 knockdown significantly enhanced RIG-I-triggered type I IFN signaling and inhibited vesicular stomatitis virus (VSV) replication both in mouse peritoneal macrophages and THP1 cells. USP14 overexpression in HeLa cells attenuated RIG-I-triggered IFN-β expression and promoted VSV replication. Besides, USP14-specific inhibitor, IU1, increased RIG-I-mediated type I IFN production and antiviral responses in vitro and in vivo. In addition, USP14 could interact with RIG-I and remove RIG-I K63-linked polyubiquitination chains. This article is the first to report that USP14 acts as a negative regulator in antiviral response through deubiquitinating K63-linked RIG-I. These findings provide insights into a potential new therapy targeting USP14 for RNA virus-related diseases.
-
USP14 promotes K63‐linked RIG‐I deubiquitination and suppresses antiviral immune responses
European Journal of Immunology, 2018Co-Authors: Hongrui Li, Zizhao Zhao, Xibao Zhao, Juan Yu, Jing Ling, Jianzhong Shen, Weilin ChenAbstract:: Retinoic acid-inducible gene I (RIG-I) is a critical RNA virus sensor that initiates antiviral immune response through K63-linked ubiquitination. In this study, we demonstrated USP14, a deubiquitinating enzyme, as a negative regulator in antiviral responses by directly deubiquitinating K63-linked RIG-I. USP14 knockdown significantly enhanced RIG-I-triggered type I IFN signaling and inhibited vesicular stomatitis virus (VSV) replication both in mouse peritoneal macrophages and THP1 cells. USP14 overexpression in HeLa cells attenuated RIG-I-triggered IFN-β expression and promoted VSV replication. Besides, USP14-specific inhibitor, IU1, increased RIG-I-mediated type I IFN production and antiviral responses in vitro and in vivo. In addition, USP14 could interact with RIG-I and remove RIG-I K63-linked polyubiquitination chains. This article is the first to report that USP14 acts as a negative regulator in antiviral response through deubiquitinating K63-linked RIG-I. These findings provide insights into a potential new therapy targeting USP14 for RNA virus-related diseases.
Michael Gale - One of the best experts on this subject based on the ideXlab platform.
-
RIG-I in RNA virus recognition.
Virology, 2015Co-Authors: Alison M Kell, Michael GaleAbstract:Antiviral immunity is initiated upon host recognition of viral products via non-self molecular patterns known as pathogen-associated molecular patterns (PAMPs). Such recognition initiates signaling cascades that induce intracellular innate immune defenses and an inflammatory response that facilitates development of the acquired immune response. The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein family are key cytoplasmic pathogen recognition receptors that are implicated in the recognition of viruses across genera and virus families, including functioning as major sensors of RNA viruses, and promoting recognition of some DNA viruses. RIG-I, the charter member of the RLR family, is activated upon binding to PAMP RNA. Activated RIG-I signals by interacting with the adapter protein MAVS leading to a signaling cascade that activates the transcription factors IRF3 and NF-κB. These actions induce the expression of antiviral gene products and the production of type I and III interferons that lead to an antiviral state in the infected cell and surrounding tissue. RIG-I signaling is essential for the control of infection by many RNA viruses. Recently, RIG-I crosstalk with other pathogen recognition receptors and components of the inflammasome has been described. In this review, we discuss the current knowledge regarding the role of RIG-I in recognition of a variety of virus families and its role in programming the adaptive immune response through cross-talk with parallel arms of the innate immune system, including how RIG-I can be leveraged for antiviral therapy.
-
the mitochondrial targeting chaperone 14 3 3e regulates a rig i translocon that mediates membrane association and innate antiviral immunity
Cell Host & Microbe, 2012Co-Authors: Stacy M Horner, Gregory A Zornetzer, Michael G Katze, Michael GaleAbstract:Summary RIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3e, as a RIG-I-binding partner and essential component of a translocation complex or "translocon" containing RIG-I, 14-3-3e, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. 14-3-3e is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. Our results define 14-3-3e as a key component of a RIG-I translocon required for innate antiviral immunity.
-
ZAPS electrifies RIG-I signaling.
Nature Immunology, 2010Co-Authors: Helene Minyi Liu, Michael GaleAbstract:ZAPS, a member of the poly(ADP-ribose) polymerase family, modulates innate antiviral immunity by boosting signaling of the RNA helicase RIG-I.
Lucy Bird - One of the best experts on this subject based on the ideXlab platform.
-
Reigning in RIG-I
Nature Reviews Immunology, 2018Co-Authors: Lucy BirdAbstract:A host-derived long non-coding RNA limits antiviral type I interferon responses by binding to and inhibiting RIG-I activation.
Xibao Zhao - One of the best experts on this subject based on the ideXlab platform.
-
usp14 promotes k63 linked rig i deubiquitination and suppresses antiviral immune responses
European Journal of Immunology, 2019Co-Authors: Hongrui Li, Zizhao Zhao, Xibao Zhao, Juan Yu, Jing Ling, Jianzhong Shen, Weilin ChenAbstract:: Retinoic acid-inducible gene I (RIG-I) is a critical RNA virus sensor that initiates antiviral immune response through K63-linked ubiquitination. In this study, we demonstrated USP14, a deubiquitinating enzyme, as a negative regulator in antiviral responses by directly deubiquitinating K63-linked RIG-I. USP14 knockdown significantly enhanced RIG-I-triggered type I IFN signaling and inhibited vesicular stomatitis virus (VSV) replication both in mouse peritoneal macrophages and THP1 cells. USP14 overexpression in HeLa cells attenuated RIG-I-triggered IFN-β expression and promoted VSV replication. Besides, USP14-specific inhibitor, IU1, increased RIG-I-mediated type I IFN production and antiviral responses in vitro and in vivo. In addition, USP14 could interact with RIG-I and remove RIG-I K63-linked polyubiquitination chains. This article is the first to report that USP14 acts as a negative regulator in antiviral response through deubiquitinating K63-linked RIG-I. These findings provide insights into a potential new therapy targeting USP14 for RNA virus-related diseases.
-
USP14 promotes K63‐linked RIG‐I deubiquitination and suppresses antiviral immune responses
European Journal of Immunology, 2018Co-Authors: Hongrui Li, Zizhao Zhao, Xibao Zhao, Juan Yu, Jing Ling, Jianzhong Shen, Weilin ChenAbstract:: Retinoic acid-inducible gene I (RIG-I) is a critical RNA virus sensor that initiates antiviral immune response through K63-linked ubiquitination. In this study, we demonstrated USP14, a deubiquitinating enzyme, as a negative regulator in antiviral responses by directly deubiquitinating K63-linked RIG-I. USP14 knockdown significantly enhanced RIG-I-triggered type I IFN signaling and inhibited vesicular stomatitis virus (VSV) replication both in mouse peritoneal macrophages and THP1 cells. USP14 overexpression in HeLa cells attenuated RIG-I-triggered IFN-β expression and promoted VSV replication. Besides, USP14-specific inhibitor, IU1, increased RIG-I-mediated type I IFN production and antiviral responses in vitro and in vivo. In addition, USP14 could interact with RIG-I and remove RIG-I K63-linked polyubiquitination chains. This article is the first to report that USP14 acts as a negative regulator in antiviral response through deubiquitinating K63-linked RIG-I. These findings provide insights into a potential new therapy targeting USP14 for RNA virus-related diseases.
Greg Wardle - One of the best experts on this subject based on the ideXlab platform.
-
recognition of 5 triphosphate by rig i helicase requires short blunt double stranded rna as contained in panhandle of negative strand virus
Immunity, 2009Co-Authors: Martin Schlee, Andreas Roth, Veit Hornung, Christina Amparo Hagmann, Vera Wimmenauer, Winfried Barchet, Christoph Coch, Markus Janke, Aleksandra Mihailovic, Greg WardleAbstract:Antiviral immunity is triggered by immunorecognition of viral nucleic acids. The cytosolic helicase RIG-I is a key sensor of viral infections and is activated by RNA containing a triphosphate at the 5' end. The exact structure of RNA activating RIG-I remains controversial. Here, we established a chemical approach for 5' triphosphate oligoribonucleotide synthesis and found that synthetic single-stranded 5' triphosphate oligoribonucleotides were unable to bind and activate RIG-I. Conversely, the addition of the synthetic complementary strand resulted in optimal binding and activation of RIG-I. Short double-strand conformation with base pairing of the nucleoside carrying the 5' triphosphate was required. RIG-I activation was impaired by a 3' overhang at the 5' triphosphate end. These results define the structure of RNA for full RIG-I activation and explain how RIG-I detects negative-strand RNA viruses that lack long double-stranded RNA but do contain blunt short double-stranded 5' triphosphate RNA in the panhandle region of their single-stranded genome.
