Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus

Dennis Berbulla Bela-ong, Brian Dall Schyth, Jun Zou, Christopher J Secombes, Niels Lorenzen

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38 Citations (Scopus)


Mechanisms that account for the high protective efficacy in teleost fish of a DNA vaccine expressing the glycoprotein (G) of Viral hemorrhagic septicemia virus (VHSV) are thought to involve early innate immune responses mediated by interferons (IFNs). Microribonucleic acids (miRNAs) are a diverse class of small (18-22 nucleotides) endogenous RNAs that potently mediate post-transcriptional silencing of a wide range of genes and are emerging as critical regulators of cellular processes, including immune responses. We have recently reported that miR-462 and miR-731 were strongly induced in rainbow trout infected with VHSV. In this study, we analyzed the expression of these miRNAs in fish following administration of the DNA vaccine and their potential functions. Quantitative RT-PCR analysis revealed the increased levels of miR-462, and miR-731 in the skeletal muscle tissue at the site of vaccine administration and in the liver of vaccinated fish relative to empty plasmid backbone-injected controls. The increased expression of these miRNAs in the skeletal muscle correlated with the increased levels of the type I interferon (IFN)-inducible gene Mx, type I IFN and IFN-γ genes at the vaccination site. Intramuscular injection of fish with either type I IFN or IFN-γ plasmid construct resulted in the upregulation of miR-462 and miR-731 at the site of injection, suggesting that the induction of these miRNAs is elicited by IFNs. To analyze the function of miR-462 and miR-731, specific silencing of these miRNAs using anti-miRNA oligonucleotides was conducted in poly I:C-treated rainbow trout fingerlings. Following VHSV challenge, anti-miRNA-injected fish had faster development of disease and higher mortalities than control fish, indicating that miR-462/731 may be involved in IFN-mediated protection conferred by poly I:C.

Original languageEnglish
Pages (from-to)3215-3222
Number of pages8
Issue number28
Early online date6 May 2015
Publication statusPublished - 22 Jun 2015

Bibliographical note

Copyright © 2015 Elsevier Ltd. All rights reserved.

The authors gratefully acknowledge the kind and able assistance of the staff of the National Veterinary Institute, Technical University of Denmark and of the Fish Health Section, Department of Animal Science, University of Aarhus. This work was supported by the Danish Research Council for Technology and Production Sciences (grants no. 26-03-0059 and 274-05-0585); the Lundbeck Foundation (grant no. 52/03); the European Commission (contract FP6007103 IMAQUANIM, and contract FP7311993 TargetFish); and by the John Birthe Meyer Foundation.


  • microRNA
  • Viral hemorrhagic septicemia virus (VHSV)
  • Rhabdovirus glycoprotein
  • DNA vaccination
  • Interferons
  • Rainbow trout


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