Fish MITA Serves as a Mediator for Distinct Fish IFN Gene Activation Dependent on IRF3 or IRF7

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	Fish MITA Serves as a Mediator for Distinct Fish IFN Gene Activation Dependent on IRF3 or IRF7
	Sun, Fan; Zhang, Yi-Bing; Liu, Ting-Kai; Shi, Jun; Wang, Bing; Gui, Jian-Fang
刊名	JOURNAL OF IMMUNOLOGY
	2011-09-01
卷号	187 期号:5 页码:2531-2539
关键词	INNATE IMMUNE-RESPONSE RIG-I PARALICHTHYS-OLIVACEUS ANTIVIRAL RESPONSES IKK-EPSILON III IFN INTERFERON VIRUS RNA EXPRESSION
ISSN号	0022-1767
通讯作者	Zhang, YB (reprint author), Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Grad Sch, Wuhan 430072, Peoples R China ; ybzhang@ihb.ac.cn ; jfgui@ihb.ac.cn
中文摘要	In mammals, cytosolic sensors retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) activate multiple signaling cascades initiating IFN-alpha/beta expression. IFN regulatory factor 3 (IRF3) is required for the activation of IFN-beta, which, in turn, primes the expression of most IFN-alpha genes by IFN-induced IRF7 through the STAT1 pathway. In fish, RIG-I overexpression inhibits virus infection by induction of IFN response; however, the subtle signaling cascade mechanism remains to be identified. In this study, we clone an ortholog of MITA, a recently identified adaptor responsible for RLR pathway, from crucian carp (Carassius auratus L.), and demonstrate its ability to suppress viral replication through IRF3/7-dependent IFN response. The pivotal signaling molecules of RLR pathway, including RIG-I, melanoma differentiation-associated gene 5, laboratory of genetics and physiology 2, and TANK-binding kinase 1, are also cloned and characterized, confirming that the RLR-mediated IFN activation is conserved from fish to mammals. Further characterization of distinct IFN gene activation reveals that zebrafish IFN1 and IFN3 are induced by the MITA pathway but are dependent on distinct transcription factors. Whereas fish IFN genes cannot be classified into IFN-alpha or IFN-beta, zebrafish IFN1 is primarily regulated by IRF3, thereby resembling that of IFN-beta, and zebrafish IFN3 is regulated by IRF7, thereby resembling of those of IFN-alpha s. In contrast with mammalian IFN-alpha/beta, zebrafish IFN1 and IFN3 are induced by the basally expressed IRF3 or IRF7, both of which are upregulated by IFN and virus infection. Collectively, these data suggest that IFN genes in fish and mammals have evolved independently to acquire a similar mechanism triggering their expression. The Journal of Immunology, 2011, 187: 2531-2539.
英文摘要	In mammals, cytosolic sensors retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) activate multiple signaling cascades initiating IFN-alpha/beta expression. IFN regulatory factor 3 (IRF3) is required for the activation of IFN-beta, which, in turn, primes the expression of most IFN-alpha genes by IFN-induced IRF7 through the STAT1 pathway. In fish, RIG-I overexpression inhibits virus infection by induction of IFN response; however, the subtle signaling cascade mechanism remains to be identified. In this study, we clone an ortholog of MITA, a recently identified adaptor responsible for RLR pathway, from crucian carp (Carassius auratus L.), and demonstrate its ability to suppress viral replication through IRF3/7-dependent IFN response. The pivotal signaling molecules of RLR pathway, including RIG-I, melanoma differentiation-associated gene 5, laboratory of genetics and physiology 2, and TANK-binding kinase 1, are also cloned and characterized, confirming that the RLR-mediated IFN activation is conserved from fish to mammals. Further characterization of distinct IFN gene activation reveals that zebrafish IFN1 and IFN3 are induced by the MITA pathway but are dependent on distinct transcription factors. Whereas fish IFN genes cannot be classified into IFN-alpha or IFN-beta, zebrafish IFN1 is primarily regulated by IRF3, thereby resembling that of IFN-beta, and zebrafish IFN3 is regulated by IRF7, thereby resembling of those of IFN-alpha s. In contrast with mammalian IFN-alpha/beta, zebrafish IFN1 and IFN3 are induced by the basally expressed IRF3 or IRF7, both of which are upregulated by IFN and virus infection. Collectively, these data suggest that IFN genes in fish and mammals have evolved independently to acquire a similar mechanism triggering their expression. The Journal of Immunology, 2011, 187: 2531-2539.
学科主题	Immunology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Immunology
研究领域[WOS]	Immunology
关键词[WOS]	INNATE IMMUNE-RESPONSE ; RIG-I ; PARALICHTHYS-OLIVACEUS ; ANTIVIRAL RESPONSES ; IKK-EPSILON ; III IFN ; INTERFERON ; VIRUS ; RNA ; EXPRESSION
收录类别	SCI
资助信息	Ministry of Science and Technology, China[2010CB126303]; National Natural Science Foundation (China)[30871922]; Ministry of Agriculture, China[2009ZX08010-021B]; Freshwater Ecology and Biotechnology Laboratory, Institute of Hydrobiology, Chinese Academy of Sciences[2009FBZ01]
语种	英语
WOS记录号	WOS:000294059500056
公开日期	2011-11-09
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/16317]
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	Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Grad Sch, Wuhan 430072, Peoples R China
推荐引用方式 GB/T 7714	Sun, Fan,Zhang, Yi-Bing,Liu, Ting-Kai,et al. Fish MITA Serves as a Mediator for Distinct Fish IFN Gene Activation Dependent on IRF3 or IRF7[J]. JOURNAL OF IMMUNOLOGY,2011,187(5):2531-2539.
APA	Sun, Fan,Zhang, Yi-Bing,Liu, Ting-Kai,Shi, Jun,Wang, Bing,&Gui, Jian-Fang.(2011).Fish MITA Serves as a Mediator for Distinct Fish IFN Gene Activation Dependent on IRF3 or IRF7.JOURNAL OF IMMUNOLOGY,187(5),2531-2539.
MLA	Sun, Fan,et al."Fish MITA Serves as a Mediator for Distinct Fish IFN Gene Activation Dependent on IRF3 or IRF7".JOURNAL OF IMMUNOLOGY 187.5(2011):2531-2539.