RLR (RIG-like receptor) mediated induction of IFN alpha/beta

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Gallus gallus
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Infectious bronchitis virus
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In human, RIG-I-like receptor (RLR) family is crucial for triggering response to cytosolic viral RNA. RLR family is composed of retinoic acid-inducible gene 1 protein (RIG-I), melanoma differentiation-associated protein 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2) [Yoneyama et al 2005].

RIG1, MDA5 and LGP2 are cytosolic multidomain proteins. They all contain a central DexD/H-box RNA helicase/adenosine triphosphatase (ATPase) domain that can bind viral RNA, and a C-terminal regulatory domain (RD) that prevents signaling in the absence of viral RNA. RIG-I and MDA5, but not LGP2, also encode two N-terminal caspase activation and recruitment domains (CARDs) that transmit the signal by binding to CARD domain of mitochondrial IFN-beta promoter stimulator protein (IPS-1; also known as MAVS, VISA or Cardif). This CARD-CARD interaction leads to production of IFN alpha/beta and pro inflammatory cytokines. LGP2 that lacks CARD motifs but binds viral RNA is believed to regulate RLR signaling, however the mechanism of the regulation remains unclear; LGP2 was reported to act as negative regulator [Yoneyama et al 2005; Komuro and Horvath 2006; Saito et al 2007], while other studies suggested that LGP2 may cooperate with RIG-1 and MDA5 in sensing certain viral RNA [Venkataraman et al 2007; Satoh et al 2010].

Primary chick embryo cells produced IFN-alpha in response to Newcastle disease virus (NDV) and produced both IFN-alpfa and IFN-beta in response to vaccinia virus or influenza A [Shwartz H et al 2004]. Those viruses have been reported to induce TLR3, RIG-1 and MDA5 signaling in mammals [Delaloye J et al 2009, Kato H et al 2006, Childs et al 2007]. Although RLR signaling is conserved among vertebrates[Sarkar D et al 2008; Zou J et al 2009 and Feng H et al 2011], analysis of chicken genome revealed only orthologs for mammalian MDA5 and LGP2, while RIG-1 gene was not identified [Sarkar D et al 2008; Zou J et al 2009; and Barber MR et al 2010].

Literature References
PubMed ID Title Journal Year
20308570 Association of RIG-I with innate immunity of ducks to influenza

Webster, RG, Barber, MR, Magor, KE, Aldridge JR, Jr

Proc Natl Acad Sci U S A 2010
18971330 Evolution of MDA-5/RIG-I-dependent innate immunity: independent evolution by domain grafting

Fisher, PB, Desalle, R, Sarkar, D

Proc Natl Acad Sci U S A 2008
16116171 Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity

Kikuchi, M, Loo, YM, Fujita, T, Matsumoto, K, Imaizumi, T, Taira, K, Miyagishi, M, Gale M, Jr, Yonehara, S, Kato, A, Yoneyama, M, Akira, S, Foy, E

J Immunol 2005
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