Inhibition of the foot-and-mouth disease virus subgenomic replicon by RNA aptamers

J Gen Virol. 2014 Dec;95(Pt 12):2649-2657. doi: 10.1099/vir.0.067751-0. Epub 2014 Aug 5.

Abstract

We have previously documented the inhibitory activity of RNA aptamers to the RNA-dependent RNA polymerase of foot-and-mouth disease virus (3D(pol)). Here we report their modification and use with a subgenomic replicon incorporating GFP (pGFP-PAC replicon), allowing replication to be monitored and quantified in real-time. GFP expression in transfected BHK-21 cells reached a maximum at approximately 8 h post-transfection, at which time change in morphology of the cells was consistent with a virus-induced cytopathic effect. However, transfection of replicon-bearing cells with a 3D(pol) aptamer RNA resulted in inhibition of GFP expression and maintenance of normal cell morphology, whereas a control aptamer RNA had little effect. The inhibition was correlated with a reduction in 3D(pol) (detected by immunoblotting) and shown to be dose dependent. The 3D(pol) aptamers appeared to be more effective than 2'-C-methylcytidine (2'CMC). Aptamers to components of the replication complex are therefore useful molecular tools for studying viral replication and also have potential as diagnostic molecules in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aptamers, Nucleotide*
  • Cell Line
  • Cricetinae
  • Foot-and-Mouth Disease Virus / genetics
  • Foot-and-Mouth Disease Virus / physiology*
  • Gene Expression Regulation, Viral / physiology
  • Genetic Engineering
  • Green Fluorescent Proteins
  • Luminescent Proteins / genetics
  • Mutagenesis
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Replicon

Substances

  • Aptamers, Nucleotide
  • Luminescent Proteins
  • RNA, Viral
  • Green Fluorescent Proteins