RIG-I样受体（RIG-I like receptors，RLRs）是一类新发现的模式识别受体，能够识别细胞质中的病毒RNA，在抗病毒天然免疫中起着重要的作用。RIG-I样受体包括3个成员, 即视黄酸诱导基因I (RIG-I)、黑色素瘤分化相关基因5 (MDA5)以及LGP2。在哺乳动物中，LGP2在RIG-I/MDA5介导的信号通路中起着负调控作用；然而也有研究表明LGP2作为RIG-I/MDA5信号通路的上游信号在抗病毒感染中起着正调控的作用。
在中国科学院水生生物研究所鱼类免疫学与寄生虫学学科组和苏格兰鱼类免疫研究中心的合作研究中，昌鸣先等揭示了RIG-I样受体MDA5和LGP2在低等脊椎动物中的功能。与哺乳动物的MDA5和LGP2相同，鱼类的MDA5和LGP2也能结合病毒双链RNA成分。然而与哺乳类的LGP2调控MDA5信号通路的功能不同，鱼类MDA5和LGP2的过表达均能增强细胞对病毒的感染；过表达MDA5对LGP2的蛋白表达没有影响，反之亦然。这说明鱼类MDA5和LGP2在抗病毒反应中可能独立发挥作用。
他们进一步研究发现，鱼类的LGP2还存在一个截短形式的剪接异构体。类似于LGP2，LGP2的剪接异构体在成纤维细胞和巨噬细胞中均可检测到表达，且其表达均能被polyI:C和重组干扰素蛋白的刺激以及单链阳性或者阴性RNA病毒的感染所诱导。LGP2的剪接异构体不具有抗病毒感染的作用，但是LGP2剪接异构体的过表达能够抑制LGP2介导的抗病毒蛋白Mx的表达，这表明LGP2剪接异构体在LGP2介导的信号传导通路中可能起着阴性调节的作用。
该研究得到国家自然科学基金重点项目（30830083）资助，主要由副研究员昌鸣先等完成，通讯作者为聂品研究员和邹钧(Jun Zou)博士，相关论文已于7月21日在线发表在《病毒学期刊》（Journal of Virology, 2011, 85: 8403-8412）。(生物谷 Bioon.com)
doi:10.1128/JVI.00445-10
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Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss)
Mingxian Chang,,Bertrand Collet, Pin Nie, Katherine Lester, Scott Campbell, Christopher J.
The retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) comprise three homologues: RIG-I, melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2). They activate the host interferon (IFN) system upon recognition of viral RNA pathogen-associated molecular patterns (PAMPs) in the cytoplasm. Bioinformatic analysis of the sequenced vertebrate genomes suggests that the cytosolic surveillance system is conserved in lower vertebrates, and recent functional studies have confirmed that RIG-I is important to fish antiviral immunity. In this study, we have identified MDA5 and LGP2 homologues from rainbow trout Oncorhynchus mykiss and an additional LGP2 variant with an incomplete C-terminal domain of RIG-I. Trout MDA5 and LGP2 were constitutively produced in fibroblast and macrophage cell lines and upregulated by poly(I:C), recombinant IFN, or infection by RNA viruses (viral hemorrhagic septicemia virus and salmon alphavirus) with a single-stranded positive or negative genome. Overexpression of MDA5 and LGP2 but not of the LGP2 variant resulted in significant accumulation of Mx transcripts in cultured cells, which correlated with a marked enhancement of protection against viral infection. These results demonstrate that both MDA5 and LGP2 are important RLRs in host surveillance against infection of both negative and positive viruses and that the LGP2 variant with a deletion of 54 amino acids at the C terminus acts as a negative regulator for LGP2-elicited antiviral signaling by competing for the viral RNA PAMPs. Interestingly, MDA5 expression was not affected by overexpressed LGP2 in transfected cells and vice versa, suggesting that they likely act in parallel as positive regulators for IFN production.