ZFIN ID: ZDB-PUB-120315-4
Identification of DreI as an Antiviral Factor Regulated by RLR Signaling Pathway
Li, S., Sun, F., Zhang, Y.B., Gui, J.F., and Zhang, Q.Y.
Date: 2012
Source: PLoS One   7(3): e32427 (Journal)
Registered Authors: Gui, Jian-Fang, Zhang, Yi-Bing
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Antiviral Agents/metabolism
  • Antiviral Agents/pharmacology
  • Base Sequence
  • Cytoplasm/metabolism
  • Gene Expression/drug effects
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism*
  • Homeodomain Proteins/pharmacology
  • Molecular Sequence Data
  • Nucleotide Motifs
  • Poly I-C/pharmacology
  • Promoter Regions, Genetic
  • Protein Transport
  • RNA Helicases/metabolism
  • Sequence Alignment
  • Signal Transduction*
  • Transcription Factor Brn-3C/genetics*
  • Transcription Factor Brn-3C/metabolism*
  • Transcription Factor Brn-3C/pharmacology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/pharmacology
PubMed: 22412872 Full text @ PLoS One
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ABSTRACT

Background

Retinoic acid-inducible gene I (RIG-I)–like receptors (RLRs) had been demonstrated to prime interferon (IFN) response against viral infection via the conserved RLR signaling in fish, and a novel fish-specific gene, the grass carp reovirus (GCRV)-induced gene 2 (Gig2), had been suggested to play important role in host antiviral response.

Methodology/Principal Findings

In this study, we cloned and characterized zebrafish Gig2 homolog (named Danio rerio Gig2-I, DreI), and revealed its antiviral role and expressional regulation signaling pathway. RT-PCR, Western blot and promoter activity assay indicate that DreI can be induced by poly I:C, spring viremia of carp virus (SVCV) and recombinant IFN (rIFN), showing that DreI is a typical ISG. Using the pivotal signaling molecules of RLR pathway, including RIG-I, MDA5 and IRF3 from crucian carp, it is found that DreI expression is regulated by RLR cascade and IRF3 plays an important role in this regulation. Furthermore, promoter mutation assay confirms that the IFN-stimulated regulatory elements (ISRE) in the 52 flanking region of DreI is essential for its induction. Finally, overexpression of DreI leads to establish a strong antiviral state against SVCV and Rana grylio virus (RGV) infection in EPC (Epithelioma papulosum cyprinid) cells.

Conclusions/Significance

These data indicate that DreI is an antiviral protein, which is regulated by RLR signaling pathway.

ADDITIONAL INFORMATION