Academic literature on the topic 'RIG-I-like receptors (RLRs)'
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Journal articles on the topic "RIG-I-like receptors (RLRs)"
1
Zheng, Wanjing, and Yoko Satta. "Functional Evolution of Avian RIG-I-Like Receptors." Genes 9, no. 9 (2018): 456. http://dx.doi.org/10.3390/genes9090456.
Full textAbstract:
RIG-I-like receptors (retinoic acid-inducible gene-I-like receptors, or RLRs) are family of pattern-recognition receptors for RNA viruses, consisting of three members: retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). To understand the role of RLRs in bird evolution, we performed molecular evolutionary analyses on the coding genes of avian RLRs using filtered predicted coding sequences from 62 bird species. Among the three RLRs, conservation score and dN/dS (ratio of nonsynonymous substitution rate over synonymous substitution rate) analyses indicate that avian MDA5 has the highest conservation level in the helicase domain but a lower level in the caspase recruitment domains (CARDs) region, which differs from mammals; LGP2, as a whole gene, has a lower conservation level than RIG-I or MDA5. We found evidence of positive selection across all bird lineages in RIG-I and MDA5 but only on the stem lineage of Galliformes in LGP2, which could be related to the loss of RIG-I in Galliformes. Analyses also suggest that selection relaxation may have occurred in LGP2 during the middle of bird evolution and the CARDs region of MDA5 contains many positively selected sites, which might explain its conservation level. Spearman’s correlation test indicates that species-to-ancestor dN/dS of RIG-I shows a negative correlation with endogenous retroviral abundance in bird genomes, suggesting the possibility of interaction between immunity and endogenous retroviruses during bird evolution.
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Takahashi, Tomoko, Yuko Nakano, Koji Onomoto, Mitsutoshi Yoneyama, and Kumiko Ui-Tei. "Virus Sensor RIG-I Represses RNA Interference by Interacting with TRBP through LGP2 in Mammalian Cells." Genes 9, no. 10 (2018): 511. http://dx.doi.org/10.3390/genes9100511.
Full textAbstract:
Exogenous double-stranded RNAs (dsRNAs) similar to viral RNAs induce antiviral RNA silencing or RNA interference (RNAi) in plants or invertebrates, whereas interferon (IFN) response is induced through activation of virus sensor proteins including Toll like receptor 3 (TLR3) or retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) in mammalian cells. Both RNA silencing and IFN response are triggered by dsRNAs. However, the relationship between these two pathways has remained unclear. Laboratory of genetics and physiology 2 (LGP2) is one of the RLRs, but its function has remained unclear. Recently, we reported that LGP2 regulates endogenous microRNA-mediated RNA silencing by interacting with an RNA silencing enhancer, TAR-RNA binding protein (TRBP). Here, we investigated the contribution of other RLRs, RIG-I and melanoma-differentiation-associated gene 5 (MDA5), in the regulation of RNA silencing. We found that RIG-I, but not MDA5, also represses short hairpin RNA (shRNA)-induced RNAi by type-I IFN. Our finding suggests that RIG-I, but not MDA5, interacts with TRBP indirectly through LGP2 to function as an RNAi modulator in mammalian cells.
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Solstad, Abigail, Octavia Hogaboam, Adriana Forero, and Emily A. Hemann. "RIG-I–like Receptor Regulation of Immune Cell Function and Therapeutic Implications." Journal of Immunology 209, no. 5 (2022): 845–54. http://dx.doi.org/10.4049/jimmunol.2200395.
Full textAbstract:
Abstract Retinoic acid–inducible gene I–like receptors (RLRs) are cytosolic RNA sensors critical for initiation of antiviral immunity. Activation of RLRs following RNA recognition leads to production of antiviral genes and IFNs for induction of broad antiviral immunity. Although the RLRs are ubiquitously expressed, much of our understanding of these molecules comes from their study in epithelial cells and fibroblasts. However, RLR activation is critical for induction of immune function and long-term protective immunity. Recent work has focused on the roles of RLRs in immune cells and their contribution to programming of effective immune responses. This new understanding of RLR function in immune cells and immune programming has led to the development of vaccines and therapeutics targeting the RLRs. This review covers recent advances in our understanding of the contribution of RLRs to immune cell function during infection and the emerging RLR-targeting strategies for induction of immunity against cancer and viral infection.
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Saito, Takeshi, and Michael Gale. "Differential recognition of double-stranded RNA by RIG-I–like receptors in antiviral immunity." Journal of Experimental Medicine 205, no. 7 (2008): 1523–27. http://dx.doi.org/10.1084/jem.20081210.
Full textAbstract:
Retinoic acid–inducible gene (RIG)-I–like receptors (RLRs) are cytosolic RNA helicases that sense viral RNA and trigger signaling pathways that induce the production of type I interferons (IFNs) and proinflammatory cytokines. RLRs recognize distinct and overlapping sets of viruses, but the mechanisms that dictate this specificity were unknown. A new study now provides evidence for size-based discrimination of double-stranded RNA (dsRNA) by RLRs and suggests how host cells recognize a variety of RNA viruses.
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Chen, Dengwang, Qinglu Ji, Jing Liu, et al. "MicroRNAs in the Regulation of RIG-I-like Receptor Signaling Pathway: Possible Strategy for Viral Infection and Cancer." Biomolecules 13, no. 9 (2023): 1344. http://dx.doi.org/10.3390/biom13091344.
Full textAbstract:
The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play a crucial role as pattern-recognition receptors within the innate immune system. These receptors, present in various cell and tissue types, serve as essential sensors for viral infections, enhancing the immune system’s capacity to combat infections through the induction of type I interferons (IFN-I) and inflammatory cytokines. RLRs are involved in a variety of physiological and pathological processes, including viral infections, autoimmune disorders, and cancer. An increasing body of research has examined the possibility of RLRs or microRNAs as therapeutic targets for antiviral infections and malignancies, despite the fact that few studies have focused on the regulatory function of microRNAs on RLR signaling. Consequently, our main emphasis in this review is on elucidating the role of microRNAs in modulating the signaling pathways of RLRs in the context of cancer and viral infections. The aim is to establish a robust knowledge base that can serve as a basis for future comprehensive investigations into the interplay between microRNAs and RIG-I, while also facilitating the advancement of therapeutic drug development.
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Schenten, Dominik, and Marvin O’Ketch. "Rig-I-Like Receptors (RLRs) regulate humoral immunity to West Nile Virus (WNV) infection." Journal of Immunology 200, no. 1_Supplement (2018): 126.15. http://dx.doi.org/10.4049/jimmunol.200.supp.126.15.
Full textAbstract:
Abstract Rig-I-like Receptors (RLRs) comprise a family of pattern recognition receptors that recognizes microbial RNA in the cytosol. RLR activation induces an anti-viral state in infected cells and leads to the release of proinflammatory cytokines and interferons. RLRs are therefore important mediators of innate immunity to many viral infections. However, the role of RLRs in the regulation of adaptive immunity is still poorly understood. Infection of MAVS-deficient mice, the essential signaling adaptor for RLRs, with West Nile Virus (WNV) results in a defective adaptive immune response. While this finding suggests a role for RLRs in the regulation of adaptive immunity to WNV, it is difficult to interpret due to a high WNV viremia in the absence of a MAVS-dependent innate immune response. In order to overcome this caveat, we have infected MAVS-deficient mice with a mutant form of WNV that is unable to assemble infectious virions and is therefore limited to a single round of infection. Here, we show that MAVS-deficient mice display increased numbers of antigen-specific CD4 T cells as well as an enlarged germinal center (GC) B cell compartment. Importantly, these mice fail to produce an effective neutralizing antibody response to WNV despite normal levels of WNV-specific antibodies. Together, these findings suggest that RLR-dependent signals regulate humoral immunity to WNV.
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Thompson, Ahna B., Amy EL Stone, and Michael J. Gale. "Identifying the interactome of the RIG-I-like Receptor LGP2." Journal of Immunology 196, no. 1_Supplement (2016): 203.18. http://dx.doi.org/10.4049/jimmunol.196.supp.203.18.
Full textAbstract:
Abstract RIG-I-like receptors (RLRs) are DEAD box helicases and cytoplasmic pathogen recognition receptors that recognize and bind to nonself/viral RNA and trigger innate antiviral immunity. RLRs are essential for detection of RNA virus infection, and include RIG-I, MDA5, and LGP2. LGP2 has been implicated as RIG-I or MDA5 cofactor to regulate their activity. We conducted a yeast 2 hybrid (Y2H) screen (using LGP2 as bait) of a human hepatic cDNA library to identify protein binding partners of LGP2. Identified proteins were validated as LGP2 interactors through overexpression and co-immunoprecipitation assays of LGP2 binding. The validated proteins were then submitted to a cell-based interferon beta-promoter-luciferase assay model of Sendai virus (SenV) infection as well as a cell based NFkB-luciferase assay of the same system. Endogenous expression of the validated proteins was then assayed through the Huh7 human hepatoma cell line system with various stimuli including viral infection with SenV and Interferon-beta treatment. Through these studies we will define the LGP2 interactome and identify proteins that act as co-factors in RLR signaling.
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Esser-Nobis, Katharina, Lauren D. Hatfield, and Michael Gale. "Spatiotemporal dynamics of innate immune signaling via RIG-I–like receptors." Proceedings of the National Academy of Sciences 117, no. 27 (2020): 15778–88. http://dx.doi.org/10.1073/pnas.1921861117.
Full textAbstract:
RIG-I, MDA5, and LGP2 comprise the RIG-I–like receptors (RLRs). RIG-I and MDA5 are essential pathogen recognition receptors sensing viral infections while LGP2 has been described as both RLR cofactor and negative regulator. After sensing and binding to viral RNA, including double-stranded RNA (dsRNA), RIG-I and MDA5 undergo cytosol-to-membrane relocalization to bind and signal through the MAVS adaptor protein on intracellular membranes, thus directing downstream activation of IRF3 and innate immunity. Here, we report examination of the dynamic subcellular localization of all three RLRs within the intracellular response to dsRNA and RNA virus infection. Observations from high resolution biochemical fractionation and electron microscopy, coupled with analysis of protein interactions and IRF3 activation, show that, in resting cells, microsome but not mitochondrial fractions harbor the central components to initiate innate immune signaling. LGP2 interacts with MAVS in microsomes, blocking the RIG-I/MAVS interaction. Remarkably, in response to dsRNA treatment or RNA virus infection, LGP2 is rapidly released from MAVS and redistributed to mitochondria, temporally correlating with IRF3 activation. We reveal that IRF3 activation does not take place on mitochondria but instead occurs at endoplasmic reticulum (ER)-derived membranes. Our observations suggest ER-derived membranes as key RLR signaling platforms controlled through inhibitory actions of LGP2 binding to MAVS wherein LGP2 translocation to mitochondria releases MAVS inhibition to facilitate RLR-mediated signaling of innate immunity.
9
Wicherska-Pawłowska, Katarzyna, Tomasz Wróbel, and Justyna Rybka. "Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) in Innate Immunity. TLRs, NLRs, and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases." International Journal of Molecular Sciences 22, no. 24 (2021): 13397. http://dx.doi.org/10.3390/ijms222413397.
Full textAbstract:
The innate immune system plays a pivotal role in the first line of host defense against infections and is equipped with patterns recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Several classes of PRRS, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) recognize distinct microbial components and directly activate immune cells. TLRs are transmembrane receptors, while NLRs and RLRs are intracellular molecules. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. The innate immune system also influences pathways involved in cancer immunosurveillance. Natural and synthetic agonists of TLRs, NLRs, or RLRs can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8+ T cells, and NK cells, into the tumor microenvironment, and are being explored as promising adjuvants in cancer immunotherapies. In this review, we provide a concise overview of TLRs, NLRs, and RLRs: their structure, functions, signaling pathways, and regulation. We also describe various ligands for these receptors and their possible application in treatment of hematopoietic diseases.
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Stone, Amy EL, Courtney Wilkins, Richard Green, and Michael J. Gale. "RIG-I-Like Receptors control unique innate immune responses following West Nile Virus infection." Journal of Immunology 196, no. 1_Supplement (2016): 203.9. http://dx.doi.org/10.4049/jimmunol.196.supp.203.9.
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Abstract RIG-I-like Receptors (RLRs), RIG-I, MDA5 and LGP2, play critical roles in innate immune defense against RNA viruses and are central to host immunity. RIG-I and MDA5 signal through CARDs to induce innate immune activation while LGP2 lacks these signaling domains but is thought to function as an RLR cofactor. During West Nile Virus (WNV) infection RIG-I and MDA5 work in tandem to initiate innate immune responses but the role of LGP2 in WNV innate immunity is not well-defined. Here we applied virologic, genetic, and bioinformatics approaches to assess innate immune signaling and global gene expression response to WNV infection in primary mouse embryonic fibroblasts (MEFs) and bone marrow derived macrophages (BMMs) from mice lacking RIG-I, MDA5, or LGP2, as well as from mice lacking both RIG-I and MDA5 (DKO). RNAseq analysis defined the distinct roles of RIG-I and MDA5 in induction of innate immune gene expression against WNV. Importantly, we found that LGP2 uniquely controls genes involved in innate immunity when compared to RIG-I and MDA5. We identify an LGP2-specific gene signature that reveals a unique, non-redundant role in innate immunity against WNV. Further, we used a multiplex cytokine assay to determine unique cytokine profiles for each RLR-deficient cell type, suggesting that these distinct transcriptomes lead to functional consequences in response to WNV. A model of unique actions of RLRs in WNV infection will be presented.
Dissertations / Theses on the topic "RIG-I-like receptors (RLRs)"
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Evans, Gareth. "RIG-I-like receptors (RLRs) : viral sensors that recognize Coxsackieviruses." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/42650/.
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The innate immune system is a vital part of the body's defences against viral pathogens. RIG-I and MDA5 belong to the retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs) family and function as cytoplasmic PRRs that are involved in the elimination of actively replicating RNA viruses. Their location and their differential responses to RNA viruses emphasises the complexity of the innate detection system. RIG-I and MDA5 contribute to antiviral signalling in different ways depending on the virus involved. Coxsackieviruses are positive sense, single-stranded RNA viruses belonging to the Enterovirus genus of the Picornaviridae family. They cause many serious diseases, including viral myocarditis (which can lead on to dilated cardiomyopathy), aseptic meningitis, and pancreatitis. In order to identify which RLR recognises these viruses and which RNA species triggers RLR activation during Coxsackievirus infection, viral ssRNA and replicative intermediates of Coxsackievirus RNA as well as synthetic dsRNA were used in this study. The results revealed that MDA5 recognises not the genomic ssRNA but the dsRNA generated by the replication of these viruses. Confocal microscopy provided unique evidence between the relationship of viral dsRNA and MDA5 while cytokine assays using HEK-MDA5 cells showed a strong immune response to Coxsackievirus and the dsRNA intermediates. This shows very strong evidence that MDA5 is a key sensor of the dsRNA intermediate of Coxsackieviruses. As RIG-Is role in Coxsackie recognition still needs to be verified Huh7 and Huh7.5.1 cells were used and showed no difference in immune response in the absence of RIG-I to Coxsackievirus infection, as well as the isolated ssRNA, suggesting that the VPg group present on the RNA blocks recognition. Furthermore immunoprecipitation experiments showed that in response to Coxsackievirus stimulation, RLRs homodimerise as well as heterodimerise with LGP2, potentially upregulating their activity as a possible mechanism for viral detection. The data presented here show a much clearer role for RLRs in Coxsackievirus infection, while opening new questions as to MDA5s role in the diseases caused by Coxsackieviruses, as well as the specifics behind dimerisation of the RLRs
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Huang, Ci-Yun, and 黃頎勻. "Determining the regulatory role of ARHGEF1 in RIG-I-like receptor (RLR)-mediated type I interferon expression." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/4ehfqf.
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碩士<br>國立臺灣大學<br>生命科學系<br>106<br>Mammalian cells express type I interferons (IFNs) that are important for innate immune defense against viral infection. Given that guanine nucleotide exchange factor GEF-H1 is the critical regulator of type I IFN expression, we sought to determine whether rho guanine nucleotide exchange factor 1 (ARHGEF1), a GEF-H1 homolog, is also able to control type I IFN expression and responses by utilizing ARHGEF1-deficient Huh7 cells and Arhgef1+/- mice. The expressions of IFNB1 and interferon-stimulated gene (ISG), MX1 were both significantly increased in RIG-I-Like Receptor (RLR) ligands-incubated or Sendai virus-infected ARHGEF1-/-Huh7 cells compared to wild-type (WT) Huh7 cells. We also observed a similar phenotype that Arhgef1+/- bone marrow-derived macrophages (BMDMs) expressed elevated amounts of Ifnb1 than WT BMDMs in response to high molecular weight (HMW) poly(I:C) stimulation. Furthermore, the production of Ifn-beta was profound enhanced in the serum of Arhgef1+/- mice administrated with HMW poly(I:C) intraperitoneally. Mechanistically, reconstitution of ARHGEF1 and different ARHGEF1 mutants into ARHGEF1-/- Huh7 cells further indicated that the negative regulation of IFNB1 expression in response to RLR stimulus was dependent on the regulator of G protein signaling (RGS), Dbl homology (DH), and Pleckstrin homology (PH) domains of ARHGEF1.
Surprisingly, while IFN-beta is known to alter cellular lipid metabolism, blocking of IFNα/β receptor signaling revealed that the decrease of lipid content and expression of sterol regulatory element-binding-protein 2 (SREBP2), a critical transcriptional factor for cholesterol synthesis, in ARHGEF1-/- Huh7 cells was not due to the elevated IFNβ expression. Taken together, our results suggest that ARHGEF1 negatively regulates RLR-mediated type I IFN expression both in vitro and in vivo and may have an additional role in the regulation of lipid metabolism.
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Watts, Tylan Aubrey. "Mechanism of MDA5 Recognition of Short RNA Ligands and Crystal Structure of PepQ." Thesis, 2013. http://hdl.handle.net/1969.1/150979.
Full textAbstract:
The innate immune pathways that stimulate the expression of cytokines and proapoptotic factors in response to infection are triggered by the activation of the cytosolic receptors retinoic acid-inducible gene I (RIG-I) and melanoma differentiationassociated gene 5 (MDA5). Activation of both receptors occurs as a result of binding to RNA. MDA5 only recognizes double stranded forms of RNA, whereas RIG-I is capable of recognizing both single and double stranded RNA. In vivo, MDA5 is known to be stimulated by long (>1 kb) strands of RNA, forming filaments along the phosphate backbone. However, the manner in which MDA5 can recognize the terminal end of its RNA ligand is uncertain.
I have examined the mechanism of binding of the MDA5 protein by comparing MDA5 binding to short (<18 bp) blunt RNA, 5’ triphosphate RNA, and RNA with a 3’ or 5’ overhang. It is shown that while the MDA5 protein regulatory domain (RD) is essential for RNA recognition, the MDA5 RD only weakly recognizes short double stranded RNA ligands with overhangs or a 5’ triphosphate group. The Cys951 residue was shown to disrupt stability of the MDA5 RD-RNA complex. Binding analyses were performed using a combination of SDS-PAGE, gel filtration analysis, and nondenaturing gel electrophoresis. In addition, structural data was gathered by crystallization of the MDA5 RD-RNA complex using X-ray crystallography. These results help to establish the manner in which MDA5 is regulated predominantly to the binding of long RNA ligands.
Also included in this document is structural data on the dimer form of the PepQ protein from E. coli. PepQ is a highly conserved proline peptidase that has a secondary activity of hydrolyzing organophosphorus triesters, toxic compounds found in many pesticides. The PepQ protein was crystallized and analyzed by X-ray diffraction. The dimer interface was clearly defined within the structure and provides insight into how the active dimer forms from the PepQ monomer.
Book chapters on the topic "RIG-I-like receptors (RLRs)"
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Oylumlu, Ece, Goksu Uzel, Lubeyne Durmus, Meric Tas, Damla Gunes, and Ceren Ciraci. "Pattern Recognition Receptor-Mediated Regulatory T Cell Functions in Diseases." In Regulatory T Cells [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.105693.
Full textAbstract:
The advent of new technologies in gene expression, immunology, molecular biology, and computational modeling studies has expedited the discovery process and provided us with a holistic view of host immune responses that are highly regulated. The regulatory mechanisms of the immune system lie not only in weakening the attacker directly but also in fortifying the defender for the development of an efficient adaptive immune response. This chapter reviews a comprehensive set of experimental and bioinformatic studies designed to deepen the current knowledge on the regulatory T cells (Tregs) in the context of Pattern Recognition Receptors (PRRs). Initially, we examined both membrane-bound Toll-like Receptors (TLRs) and C Type Lectin Receptors (CLRs); and cytosolic NOD-like Receptors (NLRs) and RIG-I like Receptors (RLRs) in Tregs. Then, we revisited the disease conditions associated with regulatory T cells by emphasizing the essential roles of PRRs. Expanding our knowledge and strategies on the regulatory mechanisms are likely to provide our best chances for long-term disease control and maintenance of homeostasis.