Cynoglossus semilaevis ISG15: A Secreted Cytokine-Like Protein That Stimulates Antiviral Immune Response in a LRGG Motif-Dependent Manner

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	Cynoglossus semilaevis ISG15: A Secreted Cytokine-Like Protein That Stimulates Antiviral Immune Response in a LRGG Motif-Dependent Manner
	Wang, Wei 1,2; Zhang, Min 1; Xiao, Zhi-zhong 1; Sun, Li 1
刊名	PLOS ONE
	2012-09-18
卷号	7 期号:9 页码:e44884
关键词	UBIQUITIN-LIKE PROTEINS GADUS-MORHUA L. BACTERIAL-INFECTION EXPRESSION ANALYSIS ATLANTIC SALMON TELEOST FISH I INTERFERON GENE ISG15 IDENTIFICATION DEFENSE
ISSN号	1932-6203
通讯作者	Sun, L (reprint author), Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China.
英文摘要	ISG15 is an ubiquitin-like protein that is induced rapidly by interferon stimulation. Like ubiquitin, ISG15 forms covalent conjugates with its target proteins in a process called ISGylation, which in mammals is known to play a role in antiviral immunity. In contrast to mammalian ISG15, the function of teleost ISG15 is unclear. In this study, we identified and analyzed the function of an ISG15 homologue, CsISG15, from tongue sole (Cynoglossus semilaevis). CsISG15 is composed of 162 residues and possesses two tandem ubiquitin-like domains and the highly conserved LRGG motif found in all known ISG15. Expression of CsISG15 occurred in a wide range of tissues and was upregulated in kidney and spleen by viral and bacterial infection. In vitro study with primary head kidney (HK) lymphocytes showed that megalocytivirus infection caused induction of CsISG15 expression and extracellular release of CsISG15 protein. Purified recombinant CsISG15 (rCsISG15) activated HK macrophages and enhanced the expression of immune genes in HK lymphocytes, both these effects, however, were significantly reduced when the conserved LRGG sequence was mutated to LAAG. Further study showed that the presence of rCsISG15 during megalocytivirus infection of HK lymphocytes reduced intracellular viral load, whereas antibody blocking of CsISG15 enhanced viral infection. Likewise, interference with CsISG15 expression by RNAi promoted viral infection. Taken together, these results indicate that CsISG15, a teleost ISG15, promotes antiviral immune response and that, unlike mammalian ISG15, CsISG15 exerts its immunoregulatory effect in the form of an unconjugated extracellular cytokine. In addition, these results also suggest a role for the LRGG motif other than that in protein conjugation.
学科主题	Multidisciplinary Sciences
收录类别	SCI
原文出处	10.1371/journal.pone.0044884
语种	英语
WOS记录号	WOS:000311313900049
公开日期	2013-09-24
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/12309]
专题	海洋研究所_实验海洋生物学重点实验室
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Wang, Wei,Zhang, Min,Xiao, Zhi-zhong,et al. Cynoglossus semilaevis ISG15: A Secreted Cytokine-Like Protein That Stimulates Antiviral Immune Response in a LRGG Motif-Dependent Manner[J]. PLOS ONE,2012,7(9):e44884.
APA	Wang, Wei,Zhang, Min,Xiao, Zhi-zhong,&Sun, Li.(2012).Cynoglossus semilaevis ISG15: A Secreted Cytokine-Like Protein That Stimulates Antiviral Immune Response in a LRGG Motif-Dependent Manner.PLOS ONE,7(9),e44884.
MLA	Wang, Wei,et al."Cynoglossus semilaevis ISG15: A Secreted Cytokine-Like Protein That Stimulates Antiviral Immune Response in a LRGG Motif-Dependent Manner".PLOS ONE 7.9(2012):e44884.