RIG-I like receptors (RLRs) are a class of pattern recognition receptors which play critical roles in initiating antiviral innate immunity through the recognition of intracellular dsRNA of infected viruses. The RLR family contains three members, retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2). In mammals, LGP2 serves as a negative mediator for RIG-I/MDA5-activated antiviral signaling, whereas positive regulatory roles of LGP2 in mediating RIG-I/MDA5-dependent antiviral responses have also been reported in LGP2-deficient mice. 

As a cooperative research between the Institute of Hydrobiology, Chinese Academy of Sciences, and the Scottish Fish Immunology Research Centre in the University of Aberdeen, Dr. Chang MingXian et al. revealed the function of MDA5 and LGP2 in teleost fish. Similar to mammalian MDA5 and LGP2, piscine MDA5 and LGP2 can also bind virus dsRNA. Differently, the overexpression of piscine MDA5 or LGP2 can enhance the resistance of cells to virus infection. Furthermore, overexpression of MDA5 had no effect on LGP2 in transfected cells and vice versa. Taken together, the study revealed that MDA5 and LGP2 act in parallel as positive regulators of the IFN response in fish cells. An additional LGP2 variant was identified, which has an incomplete C-terminal domain of RIG-I. Similar to piscine LGP2, the LGP2 variant was constitutively produced in fibroblast and macrophage cell lines and upregulated by poly (I:C), recombinant IFN, or infection of RNA viruses. Overexpression of piscine LGP2 variant had little impact on the antiviral state of the cells. However the cells cotransfected with piscine LGP2 and LGP2 variant exhibited decreased Mx expression compared with that of cells transfected with piscine LGP2 alone, demonstrating LGP2 variant with a deletion of 54 amino acids at the C terminus acts as a negative regulator for LGP2-elicited antiviral signaling. 

This research was funded by National Natural Science Foundation of China grant 30830083. A paper entitled "Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss)" was published in the journal Journal of Virology, 2011, 85: 8403-8412 (http://jvi.asm.org/cgi/content/full/85/16/8403).