Transgenic shRNA pigs reduce susceptibility to foot and mouth disease virus infection
- Shihezi University, China
- Xinjiang Academy of Animal Science, China
- Jilin University, China
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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Ethics
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).
Reviewing Editor
- Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States
Publication history
- Received: February 10, 2015
- Accepted: June 18, 2015
- Accepted Manuscript published: June 19, 2015 (version 1)
- Version of Record published: July 15, 2015 (version 2)
Copyright
© 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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Transgenic shRNA pigs reduce susceptibility to foot and mouth disease virus infection
eLife 4:e06951.
https://doi.org/10.7554/eLife.06951
Further reading
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- Cancer Biology
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A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have overall poorer outcome, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with the antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.
