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.
Article and author information
Author details
Reviewing Editor
- Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States
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).
Version 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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- Medicine
- Microbiology and Infectious Disease
Background:
End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines.
Methods:
The immune response to the COVID-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and 7 d after the second dose (V2D7) using anti-spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified 6 mo after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response.
Results:
Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development.
Conclusions:
Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance HD subjects comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of ESRD.
Funding:
F30HD102093, F30HL151182, T32HL144909, R01HL138628. This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003.
