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].

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