shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus

Abstract Foot-and-mouth disease virus (FMDV) is one of the most important animal pathogens in the world. FMDV naturally infects swine, cattle, and other cloven-hoofed animals. FMD is not adequately controlled by vaccination. An alternative strategy is to develop swine that are genetically resistant...

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Autores principales: Wenping Hu, Haixue Zheng, Qiuyan Li, Yuhang Wang, Xiangtao Liu, Xiaoxiang Hu, Wenjie Liu, Shen Liu, Zhisheng Chen, Wenhai Feng, Xuepeng Cai, Ning Li
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/28a0d6f64fde4f3b9f3e39ea16429936
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spelling oai:doaj.org-article:28a0d6f64fde4f3b9f3e39ea164299362021-12-02T16:27:44ZshRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus10.1038/s41598-021-95853-32045-2322https://doaj.org/article/28a0d6f64fde4f3b9f3e39ea164299362021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95853-3https://doaj.org/toc/2045-2322Abstract Foot-and-mouth disease virus (FMDV) is one of the most important animal pathogens in the world. FMDV naturally infects swine, cattle, and other cloven-hoofed animals. FMD is not adequately controlled by vaccination. An alternative strategy is to develop swine that are genetically resistant to infection. Here, we generated FMDV-specific shRNA transgenic cells targeting either nonstructural protein 2B or polymerase 3D of FMDV. The shRNA-positive transgenic cells displayed significantly lower viral production than that of the control cells after infection with FMDV (P < 0.05). Twenty-three transgenic cloned swine (TGCS) and nine non-transgenic cloned swine (Non-TGCS) were produced by somatic cell nuclear transfer (SCNT). In the FMDV challenge study, one TGCS was completely protected, no clinical signs, no viremia and no viral RNA in the tissues, no non-structural antibody response, another one TGCS swine recovered after showing clinical signs for two days, whereas all of the normal control swine (NS) and Non-TGCS developed typical clinical signs, viremia and viral RNA was determined in the tissues, the non-structural antibody was determined, and one Non-TGCS swine died. The viral RNA load in the blood and tissues of the TGCS was reduced in both challenge doses. These results indicated that the TGCS displayed resistance to the FMDV infection. Immune cells, including CD3+, CD4+, CD8+, CD21+, and CD172+ cells, and the production of IFN-γ were analyzed, there were no significant differences observed between the TGCS and NS or Non-TGCS, suggesting that the FMDV resistance may be mainly derived from the RNAi-based antiviral pathway. Our work provides a foundation for a breeding approach to preventing infectious disease in swine.Wenping HuHaixue ZhengQiuyan LiYuhang WangXiangtao LiuXiaoxiang HuWenjie LiuShen LiuZhisheng ChenWenhai FengXuepeng CaiNing LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Wenping Hu
Haixue Zheng
Qiuyan Li
Yuhang Wang
Xiangtao Liu
Xiaoxiang Hu
Wenjie Liu
Shen Liu
Zhisheng Chen
Wenhai Feng
Xuepeng Cai
Ning Li
shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus
description Abstract Foot-and-mouth disease virus (FMDV) is one of the most important animal pathogens in the world. FMDV naturally infects swine, cattle, and other cloven-hoofed animals. FMD is not adequately controlled by vaccination. An alternative strategy is to develop swine that are genetically resistant to infection. Here, we generated FMDV-specific shRNA transgenic cells targeting either nonstructural protein 2B or polymerase 3D of FMDV. The shRNA-positive transgenic cells displayed significantly lower viral production than that of the control cells after infection with FMDV (P < 0.05). Twenty-three transgenic cloned swine (TGCS) and nine non-transgenic cloned swine (Non-TGCS) were produced by somatic cell nuclear transfer (SCNT). In the FMDV challenge study, one TGCS was completely protected, no clinical signs, no viremia and no viral RNA in the tissues, no non-structural antibody response, another one TGCS swine recovered after showing clinical signs for two days, whereas all of the normal control swine (NS) and Non-TGCS developed typical clinical signs, viremia and viral RNA was determined in the tissues, the non-structural antibody was determined, and one Non-TGCS swine died. The viral RNA load in the blood and tissues of the TGCS was reduced in both challenge doses. These results indicated that the TGCS displayed resistance to the FMDV infection. Immune cells, including CD3+, CD4+, CD8+, CD21+, and CD172+ cells, and the production of IFN-γ were analyzed, there were no significant differences observed between the TGCS and NS or Non-TGCS, suggesting that the FMDV resistance may be mainly derived from the RNAi-based antiviral pathway. Our work provides a foundation for a breeding approach to preventing infectious disease in swine.
format article
author Wenping Hu
Haixue Zheng
Qiuyan Li
Yuhang Wang
Xiangtao Liu
Xiaoxiang Hu
Wenjie Liu
Shen Liu
Zhisheng Chen
Wenhai Feng
Xuepeng Cai
Ning Li
author_facet Wenping Hu
Haixue Zheng
Qiuyan Li
Yuhang Wang
Xiangtao Liu
Xiaoxiang Hu
Wenjie Liu
Shen Liu
Zhisheng Chen
Wenhai Feng
Xuepeng Cai
Ning Li
author_sort Wenping Hu
title shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus
title_short shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus
title_full shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus
title_fullStr shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus
title_full_unstemmed shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus
title_sort shrna transgenic swine display resistance to infection with the foot-and-mouth disease virus
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/28a0d6f64fde4f3b9f3e39ea16429936
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