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

doi:10.1016/j.isci.2022.105268

Generation of PCBP1-deficient pigs using CRISPR/Cas9-mediated gene editing

iScience. 2022 Oct 3;25(10):105268. doi: 10.1016/j.isci.2022.105268. eCollection 2022 Oct 21.

Authors

Chunyun Qi¹, Daxin Pang^{1

2

3}, Kang Yang¹, Shuyu Jiao¹, Heyong Wu¹, Chuheng Zhao¹, Lanxin Hu¹, Feng Li¹, Jian Zhou¹, Lin Yang¹, Dongmei Lv^{1

2

3}, Xiaochun Tang^{1

2

3}, Hongsheng Ouyang^{1

2

3

4}, Zicong Xie^{1

2

3}

Affiliations

¹ 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.
² Chongqing Research Institute, Jilin University, Chongqing 401123, China.
³ Chongqing Jitang Biotechnology Research Institute Co., Ltd, Chongqing, China.
⁴ Shenzhen Kingsino Technology Co., Ltd., Shenzhen, China.

Abstract

Classical swine fever virus (CSFV), a classic swine fever pathogen, causes severe economic losses worldwide. Poly (rC)-binding protein 1 (PCBP1), which interacts with N^pro 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.

Keywords: Animal biotechnology; Animal health management; Model organism; Virology.