Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss)

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	Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss)
	Chang, Mingxian 1,2; Collet, Bertrand 3; Nie, Pin 1; Lester, Katherine 3; Campbell, Scott 3; Secombes, Christopher J.2; Zou, Jun 2
刊名	JOURNAL OF VIROLOGY
	2011-08-01
卷号	85 期号:16 页码:8403-8412
关键词	RNA HELICASE LGP2 DIFFERENTIATION-ASSOCIATED GENE-5 ANTIVIRAL SIGNALING PROTEIN SALMON PANCREAS DISEASE NF-KAPPA-B RECOGNITION INTERFERON IDENTIFICATION INDUCTION DOMAIN
ISSN号	0022-538X
通讯作者	Nie, P (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China ; pinnie@ihb.ac.cn ; j.j.zou@abdn.ac.uk
中文摘要	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.
英文摘要	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.
学科主题	Virology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Virology
研究领域[WOS]	Virology
关键词[WOS]	RNA HELICASE LGP2 ; DIFFERENTIATION-ASSOCIATED GENE-5 ; ANTIVIRAL SIGNALING PROTEIN ; SALMON PANCREAS DISEASE ; NF-KAPPA-B ; RECOGNITION ; INTERFERON ; IDENTIFICATION ; INDUCTION ; DOMAIN
收录类别	SCI
资助信息	National Natural Science Foundation of China[30830083]; Royal Society of Edinburgh; EU[007103]
语种	英语
WOS记录号	WOS:000292923100043
公开日期	2011-11-09
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/16325]
专题	水生生物研究所_鱼类生物学及渔业生物技术研究中心_期刊论文
作者单位	1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 2.Univ Aberdeen, Sch Biol Sci, Scottish Fish Immunol Res Ctr, Aberdeen AB24 2TZ, Scotland 3.Marine Scotland Sci Marine Lab, Aberdeen AB11 9DB, Scotland
推荐引用方式 GB/T 7714	Chang, Mingxian,Collet, Bertrand,Nie, Pin,et al. Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss)[J]. JOURNAL OF VIROLOGY,2011,85(16):8403-8412.
APA	Chang, Mingxian.,Collet, Bertrand.,Nie, Pin.,Lester, Katherine.,Campbell, Scott.,...&Zou, Jun.(2011).Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss).JOURNAL OF VIROLOGY,85(16),8403-8412.
MLA	Chang, Mingxian,et al."Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss)".JOURNAL OF VIROLOGY 85.16(2011):8403-8412.