Higher antiviral response of RIG-I through enhancing RIG-I/MAVS-mediated signaling by its long insertion variant in zebrafish

As an intracellular pattern recognition receptor (PRR), the retinoic acid-inducible gene-I (RIG-I) is responsible for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). In the present study, an insertion variant of RIG-I with 38 amino acids inserted in...

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Bibliographic Details
Published in:Fish & shellfish immunology 2015-03, Vol.43 (1), p.13-24
Main Authors: Zou, Peng Fei, Chang, Ming Xian, Li, Ying, Huan Zhang, Shu, Fu, Jian Ping, Chen, Shan Nan, Nie, Pin
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antiviral Agents - metabolism
Cell Line
Cloning, Molecular
Danio rerio
DNA, Complementary - genetics
DNA, Complementary - metabolism
Edwardsiella tarda
Edwardsiella tarda - physiology
Enterobacteriaceae Infections - genetics
Enterobacteriaceae Infections - metabolism
Enterobacteriaceae Infections - veterinary
Enterobacteriaceae Infections - virology
Fish Diseases - genetics
Fish Diseases - metabolism
Fish Diseases - virology
Gene Expression Regulation
Interferon Type I - genetics
Interferon Type I - metabolism
Mitochondrial antiviral signaling protein
Molecular Sequence Data
Promoter Regions, Genetic
Retinoic acid-inducible gene-I
Rhabdoviridae - physiology
Rhabdoviridae Infections - genetics
Rhabdoviridae Infections - metabolism
Rhabdoviridae Infections - veterinary
Rhabdoviridae Infections - virology
RIG-Ib/MAVS-mediated signaling pathway
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sequence Alignment - veterinary
Signal Transduction
Spring viremia of carp virus
Type I IFN production
Variant
Zebrafish
Zebrafish Proteins - chemistry
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
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Summary:As an intracellular pattern recognition receptor (PRR), the retinoic acid-inducible gene-I (RIG-I) is responsible for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). In the present study, an insertion variant of RIG-I with 38 amino acids inserted in the N-terminal CARD2 domain, as well as the typical type, named as RIG-Ia and RIG-Ib respectively were identified in zebrafish. RIG-Ia and RIG-Ib were all up-regulated following the infection of a negative ssRNA virus, the Spring Viremia of Carp Virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, indicating the RLR may have a role in the recognition of both viruses and bacteria. The over-expression of RIG-Ib in cultured fish cells resulted in significant increase in type I IFN promoter activity, and in protection against SVCV infection, whereas the over-expression of RIG-Ia had no direct effect on IFN activation nor antiviral response. Furthermore, it was revealed that both RIG-Ia and RIG-Ib were associated with the downstream molecular mitochondrial antiviral signaling protein, MAVS, and interestingly RIG-Ia when co-transfected with RIG-Ib or MAVS, induced a significantly higher level of type I IFN promoter activity and the expression level of Mx and IRF7, implying that the RIG-Ia may function as an enhancer in the RIG-Ib/MAVS-mediated signaling pathway. •RIG-I was cloned in zebrafish with the finding of 38 amino acid inserted variant.•Overexpression of RIG-I induced significantly the promoter activity of type I IFN.•RIG-I and its insertion variant were all associated with the downstream MAVS.•Co-transfection of RIG-I and its variant enhanced the expression of IFN, Mx and IRF7.•The insertion variant of RIG-I may enhance RIG-I/MAVS-mediated signaling.
ISSN:1050-4648
1095-9947
DOI:10.1016/j.fsi.2014.12.001