CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance
Porcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/57132 |
| _version_ | 1818019853209960448 |
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| author | Kui Xu Yanrong Zhou Yulian Mu Zhiguo Liu Shaohua Hou Yujian Xiong Liurong Fang Changli Ge Yinghui Wei Xiuling Zhang Changjiang Xu Jingjing Che Ziyao Fan Guangming Xiang Jiankang Guo Haitao Shang Hua Li Shaobo Xiao Julang Li Kui Li |
| author_facet | Kui Xu Yanrong Zhou Yulian Mu Zhiguo Liu Shaohua Hou Yujian Xiong Liurong Fang Changli Ge Yinghui Wei Xiuling Zhang Changjiang Xu Jingjing Che Ziyao Fan Guangming Xiang Jiankang Guo Haitao Shang Hua Li Shaobo Xiao Julang Li Kui Li |
| author_sort | Kui Xu |
| collection | DOAJ |
| description | Porcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. We found no differences in meat-production or reproductive-performance traits between wild-type and DKO pigs, but detected increased iron in DKO muscle. Additional infection challenge experiments showed that DKO pigs exhibited decreased susceptibility to porcine deltacoronavirus (PDCoV), thus offering unprecedented in vivo evidence of pAPN as one of PDCoV receptors. Beyond showing that multiple gene edits can be combined in a livestock animal to achieve simultaneous resistance to two major viruses, our study introduces a valuable model for investigating infection mechanisms of porcine pathogenic viruses that exploit pAPN or CD163 for entry. |
| first_indexed | 2024-04-14T07:58:01Z |
| format | Article |
| id | doaj.art-e5a2ddc74c5d4f8fb16ab59fdc867358 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:58:01Z |
| publishDate | 2020-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e5a2ddc74c5d4f8fb16ab59fdc8673582022-12-22T02:04:59ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.57132CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performanceKui Xu0https://orcid.org/0000-0003-2804-6126Yanrong Zhou1Yulian Mu2Zhiguo Liu3https://orcid.org/0000-0003-0599-9039Shaohua Hou4Yujian Xiong5Liurong Fang6Changli Ge7Yinghui Wei8Xiuling Zhang9Changjiang Xu10Jingjing Che11Ziyao Fan12Guangming Xiang13Jiankang Guo14Haitao Shang15https://orcid.org/0000-0001-5532-8335Hua Li16Shaobo Xiao17Julang Li18Kui Li19https://orcid.org/0000-0002-5686-3898State Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Agricultural Microbiology and Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Agricultural Microbiology and Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology and Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaShandong Landsee Genetics Co., Ltd., Rizhao, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaShenzhen Kingsino Technology Co., Ltd., Shenzhen, ChinaCollege of Life Science and Engineering, Foshan University, Foshan, ChinaState Key Laboratory of Agricultural Microbiology and Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaDepartment of Animal BioSciences, University of Guelph, Ontario, CanadaState Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaPorcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. We found no differences in meat-production or reproductive-performance traits between wild-type and DKO pigs, but detected increased iron in DKO muscle. Additional infection challenge experiments showed that DKO pigs exhibited decreased susceptibility to porcine deltacoronavirus (PDCoV), thus offering unprecedented in vivo evidence of pAPN as one of PDCoV receptors. Beyond showing that multiple gene edits can be combined in a livestock animal to achieve simultaneous resistance to two major viruses, our study introduces a valuable model for investigating infection mechanisms of porcine pathogenic viruses that exploit pAPN or CD163 for entry.https://elifesciences.org/articles/57132CRISPR/Cas9PRRSVTGEVPDCoVpig |
| spellingShingle | Kui Xu Yanrong Zhou Yulian Mu Zhiguo Liu Shaohua Hou Yujian Xiong Liurong Fang Changli Ge Yinghui Wei Xiuling Zhang Changjiang Xu Jingjing Che Ziyao Fan Guangming Xiang Jiankang Guo Haitao Shang Hua Li Shaobo Xiao Julang Li Kui Li CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance eLife CRISPR/Cas9 PRRSV TGEV PDCoV pig |
| title | CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance |
| title_full | CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance |
| title_fullStr | CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance |
| title_full_unstemmed | CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance |
| title_short | CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance |
| title_sort | cd163 and papn double knockout pigs are resistant to prrsv and tgev and exhibit decreased susceptibility to pdcov while maintaining normal production performance |
| topic | CRISPR/Cas9 PRRSV TGEV PDCoV pig |
| url | https://elifesciences.org/articles/57132 |
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