and Double-knockout Pigs Are Resistant to PRRSV and TGEV and Exhibit Decreased Susceptibility to PDCoV While Maintaining Normal Production Performance

Overview

Journal Elife

Specialty Biology

Date 2020 Sep 3

PMID 32876563

Citations 67

Authors

Kui Xu

Yanrong Zhou

Yulian Mu

Zhiguo Liu

Shaohua Hou

Yujian Xiong

Liurong Fang

Changli Ge

Yinghui Wei

Xiuling Zhang

Changjiang Xu

Jingjing Che

Ziyao Fan

Guangming Xiang

Jiankang Guo

Haitao Shang

Hua Li

Shaobo Xiao

Julang Li

Kui Li

Affiliations

Soon will be listed here.

Abstract

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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