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B Activation1State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Therapeutic Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen (Zhongshan) University, Guangzhou 510275, People’s Republic of China
The antiviral immune responses were triggered by the innate immune recognition of viral infection. The type I IFNs (IFN-β and IFN-
) are the key cytokines produced upon viral infection and consequently link innate immunity with adaptive immunity. A main antiviral system in mammals is TRIF-dependent TLRs pathway, but the TRIF-independent RIG-I pathway, has also been discovered recently. In this manuscript, our study focuses on the functional characterization of zebrafish TRIF based on the comparison of its sequence and functional evolution from zebrafish to mammals. Our experimental results show that the full length cDNA of zebrafish TRIF cloned by RACE-PCR approach encodes a protein of 556 amino acids. Luciferase reporter assay confirms that zebrafish TRIF is able to induce the IFN promoter as well as activate NF-
B response promoter. The IFN induction function of zebrafish TRIF is abolished when Ala359 is mutated to Pro or His. Laser confocal microscopy shows that zebrafish TRIF is colocalized with a Golgi apparatus marker, implying its unique subcellular localization in Golgi apparatus. In zebrafish, the mRNA expression of molecules participating in RIG-I pathway are much more sensitive and specific to polyinosine-polycytidylic acid induction compared with those in TRIF-dependent antiviral pathway. The TRIF-dependent TLR4 IFN induction signaling appears not to be functional in zebrafish, since IFN expression cannot be up-regulated by LPS. These two striking findings from de novo ligand induction experiments suggest a novel antiviral mechanism in zebrafish.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Project 2007CB815800 of the National Basic Research Program (973) and Project 2006AA09Z433 of the State High-Tech Development Project (863) from the Ministry of Science and Technology of China, Project 2007DFA30840 of International S&T Cooperation Program of China, Key Project (0107) from the Ministry of Education, and Key Projects of Commission of Science and Technology of Guangdong Province and Guangzhou City. X.A. is a recipient of Outstanding Young Scientist Award of National Natural Science Foundation of China.
2 S.F. and S.C. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Anlong Xu, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, 135 Xingangxi Road, 510275, Guangzhou, People’s Republic of China. E-mail address: lssxal{at}mail.sysu.edu.cn
4 Abbreviations used in this paper: TRIF, TIR domain-containing adaptor inducing IFN-β; RIG-I, retinoic acid inducible gene I; HCV, Hepatitis C virus; TIRAP, TIR domain-containing adapter protein; IRF, IFN regulatory factor; poly(I:C), polyinosine-polycytidylic acid; EST, expressed sequence tag; UTR, untranslated regions; PI, propidium iodide; LTA, lipoteichoic acid.
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