Generation of PCBP1-deficient pigs using CRISPR/Cas9-mediated gene editing
Chunyun Qi,
Daxin Pang,
Kang Yang,
Shuyu Jiao,
Heyong Wu,
Chuheng Zhao,
Lanxin Hu,
Feng Li,
Jian Zhou,
Lin Yang,
Dongmei Lv,
Xiaochun Tang,
Hongsheng Ouyang,
Zicong Xie
Affiliations
Chunyun Qi
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Daxin Pang
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China; Chongqing Research Institute, Jilin University, Chongqing 401123, China; Chongqing Jitang Biotechnology Research Institute Co., Ltd, Chongqing, China
Kang Yang
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Shuyu Jiao
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Heyong Wu
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Chuheng Zhao
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Lanxin Hu
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Feng Li
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Jian Zhou
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Lin Yang
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China
Dongmei Lv
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China; Chongqing Research Institute, Jilin University, Chongqing 401123, China; Chongqing Jitang Biotechnology Research Institute Co., Ltd, Chongqing, China
Xiaochun Tang
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China; Chongqing Research Institute, Jilin University, Chongqing 401123, China; Chongqing Jitang Biotechnology Research Institute Co., Ltd, Chongqing, China
Hongsheng Ouyang
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China; Chongqing Research Institute, Jilin University, Chongqing 401123, China; Chongqing Jitang Biotechnology Research Institute Co., Ltd, Chongqing, China; Shenzhen Kingsino Technology Co., Ltd., Shenzhen, China
Zicong Xie
Key Lab for Zoonoses Research, Ministry of Education, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University, Changchun, Jilin Province 130062, China; Chongqing Research Institute, Jilin University, Chongqing 401123, China; Chongqing Jitang Biotechnology Research Institute Co., Ltd, Chongqing, China; Corresponding author
Summary: Classical swine fever virus (CSFV), a classic swine fever pathogen, causes severe economic losses worldwide. Poly (rC)-binding protein 1 (PCBP1), which interacts with Npro of CSFV, plays a vital role in CSFV growth. We are the first to report the generation of PCBP1-deficient pigs via gene-editing technology. The PCBP1-deficient pigs exhibited normal birth weight and reproductive-performance traits and developed normally. Viral challenge experiments indicated that primary cells isolated from F0- and F1-generation pigs exhibited significantly reduced CSFV infection. Additional mechanistic exploration further confirmed that the PCBP1 deficiency-mediated antiviral effect is related to the activation of type I interferon (IFN). Besides showing that a gene-editing strategy could be used to generate PCBP1-deficient pigs, our study introduces a valuable animal model for further investigating the infection mechanisms of CSFV that will help to develop better antiviral solutions.
