Elsevier

Virology

Volume 504, April 2017, Pages 52-62
Virology

Host microRNA-203a Is antagonistic to the progression of foot-and-mouth disease virus infection

https://doi.org/10.1016/j.virol.2017.01.019Get rights and content
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Highlights

  • Mimics of miR-203a-3p and miR-203a-5p reported to negatively regulate Sam68 expression were antagonistic to FMDV infection.

  • Both miR-203a-3p and miR-203a-5p impeded FMDV replication across multiple serotypes, most profoundly with miR-203a-5p.

  • miR-203a-5p increased Sam68 expression while decreasing Survivin; both are host factors involved in FMDV pathogenesis.

  • miR-203a-5p also appeared to target the FMDV genome as observed with reduced viral RNA levels, but not miR-203a-3p.

  • miR-203a-3p and miR-203a-5p anti-viral activity was not seen with related Picornavirus, BEV-1, suggesting FMDV-specificity.

Abstract

Sam68 was previously shown to be a critical host factor for foot-and-mouth disease virus (FMDV) replication. MicroRNA (miR) miR-203a is reportedly a negative regulator of Sam68 expression both in vitro and in vivo. Here, transfection of miR-203a-3p and miR-203a-5p mimics separately and in combination in a porcine cell line followed by FMDV infection resulted in diminished viral protein synthesis and a 4 and 6 log reduction in virus titers relative to negative controls, respectively. Unexpectedly, Sam68 expression was increased by miR-203a-5p transfection, but not miR-203a-3p. miR-203a-5p also down-regulated Survivin expression, which was predicted to play a role in FMDV infection. Moreover, miR-203a-5p but not miR-203a-3p affected a reduction in FMDV viral RNA. These effects were not replicated with a related Picornavirus, suggesting FMDV specificity. Importantly, miR-203a-3p and miR-203a-5p impaired FMDV infection across multiple FMDV serotypes. We concluded that miR-203a-3p and miR-203a-5p represent attractive potential naturally occurring bio-therapeutics against FMDV.

Keywords

MicroRNA (miRNA
MiR)
MiR-203a-3p
MiR-203a-5p
Sam68
Survivin
Foot-and-mouth disease virus (FMDV)
Bio-therapeutic

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