Int J Biol Sci 2019; 15(9):1993-2005. doi:10.7150/ijbs.34269

Research Paper

Deletion of CD163 Exon 7 Confers Resistance to Highly Pathogenic Porcine Reproductive and Respiratory Viruses on Pigs

Haitao Wang1,2,*, Liangcai Shen1,2,*, Jingyao Chen1,2, Xiaojuan Liu1,2, Tan Tan1,2, Yiqing Hu1,2, Xiaofei Bai3, Yuexin Li1,2, Kegong Tian3,4,✉, Ning Li1,2,✉, Xiaoxiang Hu1,2,✉

1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
2. National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, China.
3. National Research Center for Veterinary Medicine, Luoyang, Henan Province, China.
4. College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, China.
* Those authors contribute equally to the article.

Abstract

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is a severe infectious disease in the swine industry. PRRSV infection is mediated by porcine CD163 (pCD163). Scavenger receptor cysteine-rich domain 5 coded by exon 7 of pCD163 is essential for PRRSV infection. In this study, we generated CD163 exon 7 deleted (CD163E7D) pigs using CRISPR/Cas9 mediated homologous recombination and somatic cell nuclear transfer (SCNT). The deletion of exon 7 had no adverse effects on CD163-associated functions. Pigs were further challenged with a highly pathogenic PRRSV (HP-PRRSV) strain. The CD163E7D pigs exhibited mild clinical symptoms and had decreased viral loads in blood. All CD163E7D pigs survived the viral challenge, while all the WT pigs displayed severe symptoms, and 2 out of 6 WT pigs died during the challenge. Our results demonstrated that CD163 exon 7 deletion confers resistance to HP-PRRSV infection without impairing the biological functions of CD163.

Keywords: CD163, SRCR 5, Highly pathogenic PRRSV, CRISPR/Cas9, SCNT

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How to cite this article:
Wang H, Shen L, Chen J, Liu X, Tan T, Hu Y, Bai X, Li Y, Tian K, Li N, Hu X. Deletion of CD163 Exon 7 Confers Resistance to Highly Pathogenic Porcine Reproductive and Respiratory Viruses on Pigs. Int J Biol Sci 2019; 15(9):1993-2005. doi:10.7150/ijbs.34269. Available from http://www.ijbs.com/v15p1993.htm