A recombinant adenovirus bicistronically expressing porcine interferon-α and interferon-γ enhances antiviral effects against foot-and-mouth disease virus

Antiviral Res. 2014 Apr:104:52-8. doi: 10.1016/j.antiviral.2014.01.014. Epub 2014 Jan 29.

Abstract

Foot-and-mouth disease (FMD) is a virulent and economically costly disease in domestic livestock. Since the current vaccine available against FMD provides no protection until 7days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is by the application of anti-viral agents. The combination of recombinant adenovirus expressing type I interferon (IFN-α) and adenovirus expressing type II IFN (IFN-γ) has been reported to be an effective anti-viral treatment strategy against FMDV. Nevertheless, the recombinant adenovirus mixture may be inefficient because of the low anti-viral efficiency of IFN-γ compared to that of IFN-α. In this study, we generated a recombinant adenovirus co-expressing porcine IFN-α and IFN-γ in tandem using an FMDV 2A sequence to mediate effective cleavage of the two proteins (referred to as Ad-porcine IFN-αγ). We demonstrated that both recombinant porcine IFN-α and IFN-γ were expressed and interferon stimulated gene (ISG)s related with IFN-α and IFN-γ were induced in porcine kidney (IBRS-2) cells infected with Ad-porcine IFN-αγ. Additionally, the anti-viral effects of Ad-porcine IFN-αγ against FMDV were enhanced both in IBRS-2 cells and in CD-1 (ICR) suckling mice compared to that of adenovirus expressing only a single protein. We propose that Ad-porcine IFN-αγ could be a rapid, highly efficient, convenient anti-viral agent against FMDV.

Keywords: Anti-viral agent; Foot-and-mouth disease virus; Interferon-α; Interferon-γ; Recombinant adenovirus; Viral 2A sequence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cell Line
  • Foot-and-Mouth Disease / genetics*
  • Foot-and-Mouth Disease / mortality
  • Foot-and-Mouth Disease / virology
  • Foot-and-Mouth Disease Virus*
  • Gene Expression*
  • Genetic Vectors / genetics*
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon-alpha / genetics*
  • Interferon-gamma / genetics*
  • Mice
  • RNA, Messenger
  • Swine

Substances

  • Interferon Regulatory Factors
  • Interferon-alpha
  • RNA, Messenger
  • Interferon-gamma