Location: Foreign Animal Disease ResearchTitle: Host microRNA-203a is antagonistic to the progression of foot-and-mouth disease virus infection Author
|Gutkoska, Joseph - Oak Ridge Institute For Science And Education (ORISE)|
|Ramirez-medina, Elizabeth - Oak Ridge Institute For Science And Education (ORISE)|
|De Los Santos, Teresa|
Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2017
Publication Date: 1/31/2017
Citation: Gutkoska, J., Larocco, M.A., Ramirez-Medina, E., De Los Santos, T.B., Lawrence, P.J. 2017. Host microRNA-203a is antagonistic to the progression of foot-and-mouth disease virus infection. Virology. doi: 10.1016/j.virol.2017.01.019.
Interpretive Summary: Foot-and-mouth disease virus (FMDV) is a devastating disease of pigs and cattle, and represents a serious threat to the nation’s livestock and economy, therefore, it is imperative that new anti-viral strategies be developed against this virus. MicroRNAs are powerful molecules that regulate a variety of functions inside of cells, and can also promote or block the replication of some viruses. We have identified two different forms of a microRNA, 203a-3p and 203a-5p, that significantly block FMDV infection. They do this by changing the levels of cell proteins that the virus needs to replicate and 203a-5p directly targets the virus genome. Both forms of this microRNA could potentially be adapted to become anti-viral bio-therapeutics against FMDV.
Technical Abstract: Sam68 was previously shown to be a critical host factor for foot-and-mouth disease virus (FMDV) replication. MicroRNA (miR)-203a is a potent regulator of Sam68 expression both in vitro and in vivo. Here, we showed 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 to 6 log reduction in virus titers relative to negative controls, respectively. Interestingly, Sam68 expression was increased by miR-203a-5p transfection, but not miR-203a-3p. miR-203a also regulates Survivin, which exhibited a reduction and was predicted to play a role in FMDV infection. Importantly, miR-203a impaired FMDV infection across multiple FMDV serotypes. Despite predicted binding sites, FMDV viral RNA was not degraded in response to transfection with miR-203a-3p, but was reduced by miR-203a-5p mimics. We concluded that miR-203a-3p and miR-203a-5p represent attractive potential naturally-occurring bio-therapeutics against FMDV.