CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaing normal production performance

文献类型： 外文期刊

第一作者： Xu, Kui

作者： Xu, Kui;Mu, Yulian;Liu, Zhiguo;Hou, Shaohua;Wei, Yinghui;Zhang, Xiuling;Xu, Changjiang;Che, Jingjing;Fan, Ziyao;Xiang, Guangming;Guo, Jiankang;Li, Kui;Xu, Kui;Mu, Yulian;Liu, Zhiguo;Hou, Shaohua;Wei, Yinghui;Zhang, Xiuling;Xu, Changjiang;Che, Jingjing;Fan, Ziyao;Xiang, Guangming;Guo, Jiankang;Li, Kui;Zhou, Yanrong;Xiong, Yujian;Fang, Liurong;Xiao, Shaobo;Zhou, Yanrong;Xiong, Yujian;Fang, Liurong;Xiao, Shaobo;Ge, Changli;Shang, Haitao;Li, Hua;Li, Julang

作者机构：

期刊名称：ELIFE （ 影响因子：8.14； 五年影响因子：9.056 ）

ISSN： 2050-084X

年卷期： 2020 年 9 卷

页码：

收录情况： SCI

摘要： 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.

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