Transgenic shRNA pigs reduce susceptibility to foot and mouth disease virus infection

Elife. 2015 Jun 19:4:e06951. doi: 10.7554/eLife.06951.

Abstract

Foot-and-mouth disease virus (FMDV) is an economically devastating viral disease leading to a substantial loss to the swine industry worldwide. A novel alternative strategy is to develop pigs that are genetically resistant to infection. Here, we produce transgenic (TG) pigs that constitutively expressed FMDV-specific short interfering RNA (siRNA) derived from small hairpin RNA (shRNA). In vitro challenge of TG fibroblasts showed the shRNA suppressed viral growth. TG and non-TG pigs were challenged by intramuscular injection with 100 LD50 of FMDV. High fever, severe clinical signs of foot-and-mouth disease and typical histopathological changes were observed in all of the non-TG pigs but in none of the high-siRNA pigs. Our results show that TG shRNA can provide a viable tool for producing animals with enhanced resistance to FMDV.

Keywords: FMDV; RNAi; infectious disease; microbiology; transgenic pigs; viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified*
  • Antiviral Agents / metabolism*
  • Disease Resistance*
  • Foot-and-Mouth Disease / immunology
  • Foot-and-Mouth Disease / prevention & control*
  • Foot-and-Mouth Disease Virus / immunology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Survival Analysis
  • Swine

Substances

  • Antiviral Agents
  • RNA, Small Interfering

Grants and funding

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.