DDX58/IFIH1-mediated induction of interferon-alpha/beta

Stable Identifier
R-HSA-168928
Type
Pathway
Species
Homo sapiens
Related Species
Influenza A virus, Rotavirus, Hepatitis C Virus, Measles virus
Compartment
Synonyms
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
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RIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral double-stranded RNA (dsRNA) present within the cytoplasm (Yoneyama M & Fujita T 2007, 2008). Upon viral infection dsRNA is generated by positive-strand RNA virus families such as Flaviviridae and Coronaviridae, negative-strand RNA virus families including Orthomyxoviridae and Paramyxoviridae, and DNA virus families such as Herpesviridae and Adenoviridae (Weber F et al. 2006; Son KN et al. 2015). Functionally RIG-I and MDA5 positively regulate the IFN genes in a similar fashion, however they differ in their response to different viral species. RIG-I is essential for detecting influenza virus, Sendai virus, VSV and Japanese encephalitis virus (JEV), whereas MDA5 is essential in sensing encephalomyocarditis virus (EMCV), Mengo virus and Theiler's virus, all of which belong to the picornavirus family. RIG-I and MDA5 signalling results in the activation of IKK epsilon and (TKK binding kinase 1) TBK1, two serine/threonine kinases that phosphorylate interferon regulatory factor 3 and 7 (IRF3 and IRF7). Upon phosphorylation, IRF3 and IRF7 translocate to the nucleus and subsequently induce interferon alpha (IFNA) and interferon beta (IFNB) gene transcription (Yoneyama M et al. 2004; Yoneyama M & Fujita T 2007, 2008).

Literature References
PubMed ID Title Journal Year
18701081 Structural mechanism of RNA recognition by the RIG-I-like receptors

Fujita, T, Yoneyama, M

Immunity 2008
18989317 Viral evasion and subversion of pattern-recognition receptor signalling

Bowie, AG, Unterholzner, L

Nat Rev Immunol 2008
17942531 Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity

Martinez-Sobrido, L, Garcia-Sastre, A, Crochet, N, Loo, YM, Gill, MA, Bajwa, G, Katze, MG, Perwitasari, O, Akira, S, Fornek, J, Gale M, Jr

J Virol 2008
17683970 RIG-I family RNA helicases: cytoplasmic sensor for antiviral innate immunity

Fujita, T, Yoneyama, M

Cytokine Growth Factor Rev 2007
16214811 Regulation of the type I IFN induction: a current view

Taniguchi, T, Honda, K, Takaoka, A, Yanai, H

Int Immunol 2005
17395582 Function of RIG-I-like receptors in antiviral innate immunity

Fujita, T, Yoneyama, M

J Biol Chem 2007
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Cross References
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