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Virology Journal
Published in: Virology Journal 1/2014

Open Access 01-12-2014 | Research

Multiple microRNAs targeted to internal ribosome entry site against foot-and-mouth disease virus infection in vitro and in vivo

Authors: Yanyan Chang, Yongxi Dou, Huifang Bao, Xuenong Luo, Xuerong Liu, Kebin Mu, Zaixin Liu, Xiangtao Liu, Xuepeng Cai

Published in: Virology Journal | Issue 1/2014

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Abstract

Background

Foot-and-mouth disease virus (FMDV) causes a severe vesicular disease in domestic and wild cloven-hoofed animals. Because of the limited early protection induced by current vaccines, emergency antiviral strategies to control the rapid spread of FMD outbreaks are needed.
Here we constructed multiple microRNAs (miRNAs) targeting the internal ribosome entry site (IRES) element of FMDV and investigated the effect of IRES-specific miRNAs on FMDV replication in baby hamster kidney (BHK-21) cells and suckling mice.

Results

Four IRES-specific miRNAs significantly reduced enhanced green fluorescent protein (EGFP) expression from IRES-EGFP reporter plasmids, which were used with each miRNA expression plasmid in co-transfection of BHK-21 cells. Furthermore, treatment of BHK-21 cells with Bi-miRNA (a mixture of two miRNA expression plasmids) and Dual-miRNA (a co-cistronic expression plasmid containing two miRNA hairpin structures) induced more efficient and greater inhibition of EGFP expression than did plasmids carrying single miRNA sequences.
Stably transformed BHK-21 cells and goat fibroblasts with an integrating IRES-specific Dual-miRNA were generated, and real-time quantitative RT-PCR showed that the Dual-miRNA was able to effectively inhibit the replication of FMDV (except for the Mya98 strain) in the stably transformed BHK-21 cells.
The Dual-miRNA plasmid significantly delayed the deaths of suckling mice challenged with 50× and 100× the 50% lethal dose (LD50) of FMDV vaccine strains of three serotypes (O, A and Asia 1), and induced partial/complete protection against the prevalent PanAsia-1 and Mya98 strains of FMDV serotype O.

Conclusion

These data demonstrate that IRES-specific miRNAs can significantly inhibit FMDV infection in vitro and in vivo.
Appendix
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Metadata
Title
Multiple microRNAs targeted to internal ribosome entry site against foot-and-mouth disease virus infection in vitro and in vivo
Authors
Yanyan Chang
Yongxi Dou
Huifang Bao
Xuenong Luo
Xuerong Liu
Kebin Mu
Zaixin Liu
Xiangtao Liu
Xuepeng Cai
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2014
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-11-1

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