scholarly journals Functional Evolution of Avian RIG-I-Like Receptors

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 456 ◽  
Author(s):  
Wanjing Zheng ◽  
Yoko Satta
Keyword(s):  
Retinoic Acid ◽  
Substitution Rate ◽  
Conservation Score ◽  
Bird Species ◽  
Nonsynonymous Substitution ◽  
Endogenous Retroviruses ◽  
Helicase Domain ◽  
Bird Evolution ◽  
Conservation Level ◽  
Inducible Gene

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.

Retinoic acid-inducible gene-I is induced by interleukin-1beta in cultured human gingival fibroblasts

2005 ◽  
Vol 20 (1) ◽  
pp. 47-50 ◽  
Author(s):  
H. Sakaki ◽  
T. Imaizumi ◽  
T. Matsumiya ◽  
A. Kusumi ◽  
H. Nakagawa ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Interleukin 1Beta ◽  
Inducible Gene

Activation of Retinoic Acid Inducible Gene (RIG-I) by Nucleotide Analogs: A Potential Novel Mechanism for Antiviral Discovery

2010 ◽  
Vol 86 (1) ◽  
pp. A35 ◽  
Author(s):  
Radhakrishnan Iyer ◽  
John Coughlin ◽  
Seetharamaiyer Padmanabhan ◽  
Brent Korba ◽  
Sua Myong
Keyword(s):  
Retinoic Acid ◽  
Nucleotide Analogs ◽  
Inducible Gene

scholarly journals Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziqi Zou ◽  
Mengyao Li ◽  
Yunlian Zhou ◽  
Jiaying Li ◽  
Ting Pan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Retinoic Acid ◽  
Viral Infection ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Rna Virus ◽  
Type I ◽  
Factor Α ◽  
Necrosis Factor ◽  
Inducible Gene

A systematic and flexible immunoregulatory network is required to ensure the proper outcome of antiviral immune signaling and maintain homeostasis during viral infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been extensively studied in inflammatory response, apoptosis, and cancer. However, the function of TIPE2 in antiviral innate immunity is poorly clarified. In this study, we reported that the expression of TIPE2 declined at the early period and then climbed up in macrophages under RNA virus stimulation. Knockout of TIPE2 in the macrophages enhanced the antiviral capacity and facilitated type I interferon (IFN) signaling after RNA viral infection both in vitro and in vivo. Consistently, overexpression of TIPE2 inhibited the production of type I IFNs and pro-inflammatory cytokines, and thus promoted the viral infection. Moreover, TIPE2 restrained the activation of TBK1 and IRF3 in the retinoic acid inducible gene-I (RIG-I)-like receptors (RLR) signaling pathway by directly interacting with retinoic acid inducible gene-I (RIG-I). Taken together, our results suggested that TIPE2 suppresses the type I IFN response induced by RNA virus by targeting RIG-I and blocking the activation of downstream signaling. These findings will provide new insights to reveal the immunological function of TIPE2 and may help to develop new strategies for the clinical treatment of RNA viral infections.

scholarly journals Ataxia Telangiectasia Mutated Kinase Mediates NF-κB Serine 276 Phosphorylation and Interferon Expression via the IRF7-RIG-I Amplification Loop in Paramyxovirus Infection

2014 ◽  
Vol 89 (5) ◽  
pp. 2628-2642 ◽  
Author(s):  
Ling Fang ◽  
Sanjeev Choudhary ◽  
Bing Tian ◽  
Istvan Boldogh ◽  
Chunying Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Retinoic Acid ◽  
Dna Damage Response ◽  
Type I ◽  
Regulatory Factor ◽  
Ataxia Telangiectasia Mutated ◽  
Damage Response ◽  
Amplification Loop ◽  
Inducible Gene

ABSTRACTRespiratory syncytial virus (RSV) is a primary etiological agent of childhood lower respiratory tract disease. Molecular patterns induced by active infection trigger a coordinated retinoic acid-inducible gene I (RIG-I)-Toll-like receptor (TLR) signaling response to induce inflammatory cytokines and antiviral mucosal interferons. Recently, we discovered a nuclear oxidative stress-sensitive pathway mediated by the DNA damage response protein, ataxia telangiectasia mutated (ATM), in cytokine-induced NF-κB/RelA Ser 276 phosphorylation. Here we observe that ATM silencing results in enhanced single-strand RNA (ssRNA) replication of RSVand Sendai virus, due to decreased expression and secretion of type I and III interferons (IFNs), despite maintenance of IFN regulatory factor 3 (IRF3)-dependent IFN-stimulated genes (ISGs). In addition to enhanced oxidative stress, RSV replication enhances foci of phosphorylated histone 2AX variant (γH2AX), Ser 1981 phosphorylation of ATM, and IKKγ/NEMO-dependent ATM nuclear export, indicating activation of the DNA damage response. ATM-deficient cells show defective RSV-induced mitogen and stress-activated kinase 1 (MSK-1) Ser 376 phosphorylation and reduced RelA Ser 276 phosphorylation, whose formation is required for IRF7 expression. We observe that RelA inducibly binds the native IFN regulatory factor 7 (IRF7) promoter in an ATM-dependent manner, and IRF7 inducibly binds to the endogenous retinoic acid-inducible gene I (RIG-I) promoter. Ectopic IRF7 expression restores RIG-I expression and type I/III IFN expression in ATM-silenced cells. We conclude that paramyxoviruses trigger the DNA damage response, a pathway required for MSK1 activation of phospho Ser 276 RelA formation to trigger the IRF7-RIG-I amplification loop necessary for mucosal IFN production. These data provide the molecular pathogenesis for defects in the cellular innate immunity of patients with homozygous ATM mutations.IMPORTANCERNA virus infections trigger cellular response pathways to limit spread to adjacent tissues. This “innate immune response” is mediated by germ line-encoded pattern recognition receptors that trigger activation of two, largely independent, intracellular NF-κB and IRF3 transcription factors. Downstream, expression of protective antiviral interferons is amplified by positive-feedback loops mediated by inducible interferon regulatory factors (IRFs) and retinoic acid inducible gene (RIG-I). Our results indicate that a nuclear oxidative stress- and DNA damage-sensing factor, ATM, is required to mediate a cross talk pathway between NF-κB and IRF7 through mediating phosphorylation of NF-κB. Our studies provide further information about the defects in cellular and innate immunity in patients with inherited ATM mutations.

An optimized retinoic acid-inducible gene I agonist M8 induces immunogenic cell death markers in human cancer cells and dendritic cell activation

2019 ◽  
Vol 68 (9) ◽  
pp. 1479-1492 ◽  
Author(s):  
Luciano Castiello ◽  
Alessandra Zevini ◽  
Elisabetta Vulpis ◽  
Michela Muscolini ◽  
Matteo Ferrari ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Dendritic Cell ◽  
Cancer Cells ◽  
Cell Activation ◽  
Human Cancer ◽  
Immunogenic Cell Death ◽  
Dendritic Cell Activation ◽  
Human Cancer Cells ◽  
Inducible Gene

scholarly journals Mismatches in the Influenza A Virus RNA Panhandle Prevent Retinoic Acid-Inducible Gene I (RIG-I) Sensing by Impairing RNA/RIG-I Complex Formation

2015 ◽  
Vol 90 (1) ◽  
pp. 586-590 ◽  
Author(s):  
Stéphanie Anchisi ◽  
Jessica Guerra ◽  
Geneviève Mottet-Osman ◽  
Dominique Garcin
Keyword(s):  
Influenza Virus ◽  
Retinoic Acid ◽  
Complex Formation ◽  
Influenza A Virus ◽  
Rna Structure ◽  
Influenza A ◽  
Double Stranded Rna ◽  
Virus Rna ◽  
Inducible Gene

Influenza virus RNA (vRNA) promoter panhandle structures are believed to be sensed by retinoic acid-inducible gene I (RIG-I). The occurrence of mismatches in this double-stranded RNA structure raises questions about their effect on innate sensing. Our results suggest that mismatches in vRNA promoters decrease binding to RIG-Iin vivo, affecting RNA/RIG-I complex formation and preventing RIG-I activation. These results can be inferred to apply to other viruses and suggest that mismatches may represent a general viral strategy to escape RIG-I sensing.

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