TY - JOUR TI - CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance AU - Xu, Kui AU - Zhou, Yanrong AU - Mu, Yulian AU - Liu, Zhiguo AU - Hou, Shaohua AU - Xiong, Yujian AU - Fang, Liurong AU - Ge, Changli AU - Wei, Yinghui AU - Zhang, Xiuling AU - Xu, Changjiang AU - Che, Jingjing AU - Fan, Ziyao AU - Xiang, Guangming AU - Guo, Jiankang AU - Shang, Haitao AU - Li, Hua AU - Xiao, Shaobo AU - Li, Julang AU - Li, Kui A2 - Davenport, Miles P A2 - Carette, Jan E A2 - Tuggle, Christopher K VL - 9 PY - 2020 DA - 2020/09/02 SP - e57132 C1 - eLife 2020;9:e57132 DO - 10.7554/eLife.57132 UR - https://doi.org/10.7554/eLife.57132 AB - 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. KW - CRISPR/Cas9 KW - PRRSV KW - TGEV KW - PDCoV KW - pig JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -