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

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. DOI: http://dx.doi.org/10.7554/eLife.06951.001