%0 Journal Article
%T Generation of Pigs Resistant to Highly Pathogenic-Porcine Reproductive and Respiratory Syndrome Virus through Gene Editing of CD163
%A Dawei Yu
%A Dengke Pan
%A Haitao Wang
%A Jianhui Bai
%A Jie Zhong
%A Jingyao Chen
%A Kegong Tian
%A Linlin Zhang
%A Linyuan Ma
%A Man Hu
%A Ning Li
%A Tan Tan
%A Tao Feng
%A Wenjie Liu
%A Xiaofei Bai
%A Xiaojuan Liu
%A Xiaoxiang Hu
%A Yaofeng Zhao
%A Yiming Xing
%A Yiqing Hu
%A Yunlong Zou
%A Zhaolin Sun
%J International Journal of Biological Sciences
%D 2019
%R 10.7150/ijbs.25862
%X Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease and the most economically important disease of the swine industry worldwide. Highly pathogenic-PRRS virus (HP-PRRSV) is a variant of PRRSV, which caused high morbidity and mortality. Scavenger receptor CD163, which contains nine scavenger receptor cysteine-rich (SRCR) domains, is a key entry mediator for PRRSV. A previous study demonstrated that SRCR domain 5 (SRCR5), encoded by exon 7, was essential for PRRSV infection in vitro. Here, we substituted exon 7 of porcine CD163 with the corresponding exon of human CD163-like 1 (hCD163L1) using a CRISPR/Cas9 system combined with a donor vector. In CD163Mut/Mut pigs, modifying CD163 gene had no adverse effects on hemoglobin-haptoglobin (Hb-Hp) complex clearance or erythroblast growth. In vitro infection experiments showed that the CD163 mutant strongly inhibited HP-PRRSV replication by inhibiting virus uncoating and genome release. Compared to wild-type (WT) pigs in vivo, HP-PRRSV-infected CD163Mut/Mut pigs showed a substantially decreased viral load in blood and relief from PRRSV-induced fever. While all WT pigs were dead, there of four CD163Mut/Mut pigs survived and recovered at the termination of the experiment. Our data demonstrated that modifying CD163 remarkably inhibited PRRSV replication and protected pigs from HP-PRRSV infection, thus establishing a good foundation for breeding PRRSV-resistant pigs via gene editing technology.
%K HP-PRRSV
%K CD163
%K CRISPR/Cas9
%U http://www.ijbs.com/v15p0481.htm