Transgenic shRNA pigs reduce susceptibility to foot and mouth disease virus infection
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 siRNA derived from small hairpin RNA (shRNA). In vitro challenge of TG fibroblasts showed the shRNA suppressed viral growth. TG and non-transgenic (Non-TG) pigs were challenged by intramuscular injection with 100 LD50 of FMDV. High fever, severe clinical sign of FMD 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 transgenic shRNA can provide a viable tool for producing animals with enhanced resistance to FMDV.
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Animal experimentation: All experiments involving animals were conducted under the protocol approved by the Animal Care and Use Committee of Shihezi University (SU-ACUC-12031).
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© 2015, Hu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Microbiology and Infectious Disease
Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream of apicomplexan PKG and PKA; however, less is known about the global integration of AGC kinase signaling cascades. Here, conditional genetics coupled to unbiased proteomics demonstrates that SPARK complexes with an elongin-like protein to regulate the stability of PKA and PKG in the model apicomplexan Toxoplasma gondii. Defects attributed to SPARK depletion develop after PKG and PKA are down-regulated. Parasites lacking SPARK differentiate into the chronic form of infection, which may arise from reduced activity of a coccidian-specific PKA ortholog. This work delineates the signaling topology of AGC kinases that together control transitions within the asexual cycle of this important family of parasites.