Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines

2006 ◽  
Vol 8 (8) ◽  
pp. 2013-2020 ◽  
Author(s):  
Jukka Sirén ◽  
Tadaatsu Imaizumi ◽  
Devanand Sarkar ◽  
Taija Pietilä ◽  
Diana L. Noah ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Induced Expression ◽  
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.

scholarly journals Effect of Forsythiaside A on the RLRs Signaling Pathway in the Lungs of Mice Infected with the Influenza A Virus FM1 Strain

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4219
Author(s):  
Xiao Zheng ◽  
Yingjie Fu ◽  
Shan-Shan Shi ◽  
Sha Wu ◽  
Yuqi Yan ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Signaling Pathway ◽  
Influenza A Virus ◽  
Immune Cells ◽  
Influenza A ◽  
T Cell Subsets ◽  
Physical Parameters ◽  
Gene And Protein Expression ◽  
Forsythia Suspensa ◽  
Inducible Gene

Forsythiaside A, a phenylethanoid glycoside monomer extracted from Forsythia suspensa, shows anti-inflammatory, anti-infective, anti-oxidative, and antiviral pharmacological effects. The precise mechanism underlying the antiviral action of forsythiaside A is not completely clear. Therefore, in this study, we aimed to determine whether the anti-influenza action of forsythiaside A occurs via the retinoic acid-inducible gene-I–like receptors (RLRs) signaling pathway in the lung immune cells. Forsythiaside A was used to treat C57BL/6J mice and MAVS−/− mice infected with mouse-adapted influenza A virus FM1 (H1N1, A/FM1/1/47 strain), and the physical parameters (body weight and lung index) and the expression of key factors in the RLRs/NF-κB signaling pathway were evaluated. At the same time, the level of virus replication and the ratio of Th1/Th2 and Th17/Treg of T cell subsets were measured. Compared with the untreated group, the weight loss in the forsythiaside A group in the C57BL/6J mice decreased, and the histopathological sections showed less inflammatory damage after the infection with the influenza A virus FM1 strain. The gene and protein expression of retinoic acid-inducible gene-I (RIG-I), MAVS, and NF-κB were significantly decreased in the forsythiaside A group. Flow cytometry showed that Th1/Th2 and Th17/Treg differentiated into Th2 cells and Treg cells, respectively, after treatment with forsythiaside A. In conclusion, forsythiaside A reduces the inflammatory response caused by influenza A virus FM1 strain in mouse lungs by affecting the RLRs signaling pathway in the mouse lung immune cells.

scholarly journals Inhibition of Retinoic Acid-Inducible Gene I-Mediated Induction of Beta Interferon by the NS1 Protein of Influenza A Virus

2006 ◽  
Vol 81 (2) ◽  
pp. 514-524 ◽  
Author(s):  
Masaki Mibayashi ◽  
Luis Martínez-Sobrido ◽  
Yueh-Ming Loo ◽  
Washington B. Cárdenas ◽  
Michael Gale ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Influenza A Virus ◽  
Transcriptional Activation ◽  
Influenza A ◽  
Rna Virus ◽  
Nonstructural Protein ◽  
Ns1 Protein ◽  
Beta Interferon ◽  
Nonstructural Protein 1 ◽  
Inducible Gene

ABSTRACT The retinoic acid-inducible gene I product (RIG-I) has been identified as a cellular sensor of RNA virus infection resulting in beta interferon (IFN-β) induction. However, many viruses are known to encode viral products that inhibit IFN-β production. In the case of influenza A virus, the viral nonstructural protein 1 (NS1) prevents the induction of the IFN-β promoter by inhibiting the activation of transcription factors, including IRF-3, involved in IFN-β transcriptional activation. The inhibitory properties of NS1 appear to be due at least in part to its binding to double-stranded RNA (dsRNA), resulting in the sequestration of this viral mediator of RIG-I activation. However, the precise effects of NS1 on the RIG-I-mediated induction of IFN-β have not been characterized. We now report that the NS1 of influenza A virus interacts with RIG-I and inhibits the RIG-I-mediated induction of IFN-β. This inhibition was apparent even when a mutant RIG-I that is constitutively activated (in the absence of dsRNA) was used to trigger IFN-β production. Coexpression of RIG-I, its downstream signaling partner, IPS-1, and NS1 resulted in increased levels of RIG-I and NS1 within an IPS-1-rich, solubilization-resistant fraction after cell lysis. These results suggest that RIG-I, IPS-1, and NS1 become part of the same complex. Consistent with this idea, NS1 was also found to inhibit IFN-β promoter activation by IPS-1 overexpression. Our results indicate that, in addition to sequestering dsRNA, the NS1 of influenza A virus binds to RIG-I and inhibits downstream activation of IRF-3, preventing the transcriptional induction of IFN-β.

scholarly journals Interactions between the Influenza A Virus RNA Polymerase Components and Retinoic Acid-Inducible Gene I

2014 ◽  
Vol 88 (18) ◽  
pp. 10432-10447 ◽  
Author(s):  
W. Li ◽  
H. Chen ◽  
T. Sutton ◽  
A. Obadan ◽  
D. R. Perez
Keyword(s):  
Retinoic Acid ◽  
Rna Polymerase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Virus Rna ◽  
Inducible Gene

scholarly journals FKBP5 Regulates RIG-I-Mediated NF-κB Activation and Influenza A Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 672
Author(s):  
Wenzhuo Hao ◽  
Lingyan Wang ◽  
Shitao Li
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Social Impact ◽  
Respiratory Pathogen ◽  
Innate Immune Responses ◽  
Interferon Stimulated Genes ◽  
Fk506 Binding Protein ◽  
Ikk Complex ◽  
Inducible Gene

Influenza A virus (IAV) is a highly transmissible respiratory pathogen and is a constant threat to global health with considerable economic and social impact. Influenza viral RNA is sensed by host pattern recognition receptors (PRRs), such as the Toll-like receptor 7 (TLR7) and retinoic acid-inducible gene I (RIG-I). The activation of these PRRs instigates the interferon regulatory factor (IRF) and nuclear factor kappa B (NF-κB) signaling pathways that induce the expression of interferon-stimulated genes (ISGs) and inflammatory genes. FK506-binding protein 5 (FKBP5) has been implied in the IκBα kinase (IKK) complex. However, the role of FKBP5 in the RIG-I signaling and IAV infection is not well elucidated. Here, we demonstrate that the knockout of FKBP5 increases IAV infection. Furthermore, FKBP5 binds IKKα, which is critical for RIG-I-induced innate immune responses and ISG expression. Taken together, FKBP5 is a novel anti-influenza host factor that restricts IAV infection by the activation of RIG-I-mediated NF-κB signaling.

scholarly journals Cytoplasm and Beyond: Dynamic Innate Immune Sensing of Influenza A Virus by RIG-I

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
GuanQun Liu ◽  
Yan Zhou
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Innate Immune ◽  
Cytoplasmic Localization ◽  
Full Spectrum ◽  
Cytoplasmic Rna ◽  
Immune Sensing ◽  
Rna Ligands ◽  
Innate Immune Sensing ◽  
Inducible Gene

ABSTRACTInnate immune sensing of influenza A virus (IAV) requires retinoic acid-inducible gene I (RIG-I), a fundamental cytoplasmic RNA sensor. How RIG-I’s cytoplasmic localization reconciles with the nuclear replication nature of IAV is poorly understood. Recent findings provide advanced insights into the spatiotemporal RIG-I sensing of IAV and highlight the contribution of various RNA ligands to RIG-I activation. Understanding a compartment-specific RIG-I-sensing paradigm would facilitate the identification of the full spectrum of physiological RIG-I ligands produced during IAV infection.

scholarly journals The p150 Isoform of ADAR1 Blocks Sustained RLR signaling and Apoptosis during Influenza Virus Infection

2020 ◽  
Author(s):  
Olivia A. Vogel ◽  
Julianna Han ◽  
Chieh-Yu Liang ◽  
Santhakumar Manicassamy ◽  
Jasmine T. Perez ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Retinoic Acid ◽  
Rna Editing ◽  
Influenza A ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Negative Regulators ◽  
Editing Activity ◽  
Editing Enzyme ◽  
Inducible Gene

AbstractSignaling through retinoic acid inducible gene I (RIG-I) like receptors (RLRs) is tightly regulated, with activation occurring upon sensing of viral nucleic acids, and suppression mediated by negative regulators. Under homeostatic conditions aberrant activation of melanoma differentiation-associated protein-5 (MDA5) is prevented through editing of endogenous dsRNA by RNA editing enzyme Adenosine Deaminase Acting on RNA (ADAR1). In addition, ADAR1 is postulated to play proviral and antiviral roles during viral infections that are dependent or independent of RNA editing activity. Here, we investigated the importance of ADAR1 isoforms in modulating influenza A virus (IAV) replication and revealed the opposing roles for ADAR1 isoforms, with the nuclear p110 isoform restricting versus the cytoplasmic p150 isoform promoting IAV replication. Importantly, we demonstrate that p150 is critical for preventing sustained RIG-I signaling, as p150 deficient cells showed increased IFN-β expression and apoptosis during IAV infection, independent of RNA editing activity. Taken together, the p150 isoform of ADAR1 is important for preventing sustained RIG-I induced IFN-β expression and apoptosis during viral infection.

scholarly journals Virus-induced expression of retinoic acid inducible gene-I and melanoma differentiation-associated gene 5 in the cochlear sensory epithelium

2013 ◽  
Vol 15 (8-9) ◽  
pp. 592-598 ◽  
Author(s):  
Yushi Hayashi ◽  
Koji Onomoto ◽  
Ryo Narita ◽  
Mitsutoshi Yoneyama ◽  
Hiroki Kato ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Sensory Epithelium ◽  
Induced Expression ◽  
Inducible Gene

Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein

Virus Genes ◽  
2016 ◽  
Vol 52 (6) ◽  
pp. 759-767 ◽  
Author(s):  
Hongren Qu ◽  
Jing Li ◽  
Limin Yang ◽  
Lei Sun ◽  
Wenjun Liu ◽  
...  
Keyword(s):  
Viral Replication ◽  
Influenza A Virus ◽  
Influenza A ◽  
Induced Expression

Antiviral effect of polyphenol-enriched extract of Rumex Acetosa L. against Influenza A virus

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
A Derksen ◽  
W Hafezi ◽  
A Hensel ◽  
J Kühn
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Effect ◽  
Rumex Acetosa
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