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

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

doi:10.7554/elife.57132

Cited by 99 publications

(86 citation statements)

References 49 publications

(66 reference statements)

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“…Double gene-knockout pigs were generated, which lacked CD163 and pAPN. Pigs were completely resistant to PRRSV-2 and TGEV infection, which demonstrates how pigs can be made resistant to more than one pathogen [42].…”

Section: In Vivo Evidence For Cd163 As the Receptor For Prrsvmentioning

confidence: 92%

“…All of these receptors were initially characterized using in vitro model systems. The incorporation of studies using genetically modified pigs shows that CD163 is the only putative receptor that is necessary and sufficient for infection [36][37][38][39][40][41][42]. The precise role of CD169 remains unclear but may function as a co-factor for viral internalization [43,44].…”

Section: Viral Entry Mediators and Putative Receptors For Prrsvmentioning

confidence: 99%

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Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control

Rowland

Yoo

2021

Vaccines

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Cellular receptors play a critical role in viral infection. At least seven cellular molecules have been identified as putative viral entry mediators for porcine reproductive and respiratory syndrome virus (PRRSV). Accumulating data indicate that among these candidates, sialoadhesin (CD)163, a cysteine-rich scavenger receptor on macrophages, is the major receptor for PRRSV. This review discusses the recent advances and understanding of the entry of PRRSV into cells, viral pathogenesis in CD163 gene-edited swine, and CD163 as a potential target of receptor–ligand for the control of PRRS.

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Section: In Vivo Evidence For Cd163 As the Receptor For Prrsvmentioning

confidence: 92%

Section: Viral Entry Mediators and Putative Receptors For Prrsvmentioning

confidence: 99%

Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control

Rowland

Yoo

2021

Vaccines

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“…Such gene-edited cells have accelerated SCNT-mediated production of genetically modified pigs. Gene editors also facilitate multiple gene editing and knock-in of exogenous genes; hence, double- [ 36 , 37 , 38 ], triple- [ 39 , 40 , 41 ], and quadruple-gene-edited pigs [ 42 ] and knock-in pigs [ 43 , 44 ] have been generated using the SCNT technique. Following appropriate selection of donor cells after gene editing, the delivered piglets carry the desired genotypes.…”

Section: Methods For Generation Of Genetically Modified Pigs Using Gementioning

confidence: 99%

Current status of the application of gene editing in pigs

2021

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Genetically modified animals, especially rodents, are widely used in biomedical research. However, non-rodent models are required for efficient translational medicine and preclinical studies. Owing to the similarity in the physiological traits of pigs and humans, genetically modified pigs may be a valuable resource for biomedical research. Somatic cell nuclear transfer (SCNT) using genetically modified somatic cells has been the primary method for the generation of genetically modified pigs. However, site-specific gene modification in porcine cells is inefficient and requires laborious and time-consuming processes. Recent improvements in gene-editing systems, such as zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas) system, represent major advances. The efficient introduction of site-specific modifications into cells via gene editors dramatically reduces the effort and time required to generate genetically modified pigs. Furthermore, gene editors enable direct gene modification during embryogenesis, bypassing the SCNT procedure. The application of gene editors has progressively expanded, and a range of strategies is now available for porcine gene engineering. This review provides an overview of approaches for the generation of genetically modified pigs using gene editors, and highlights the current trends, as well as the limitations, of gene editing in pigs.

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“…However, lung fibroblast-like cells derived from these animals supported a high level of PDCoV infection indicating that APN is a dispensible receptor for PDCoV (Stoian et al, 2020). Double-gene-knockout (DKO) pigs containing KOs for known receptor proteins CD163 and pAPN are reported to be completely resistant to genotype 2 PRRSV and TGEV (Xu et al, 2020). Additional infection challenge experiments have shown that these DKO pigs exhibit decreased susceptibility to PDCoV, thus providing in vivo evidence that pAPN as likely to be one of PDCoV receptors.…”

Section: Improving Health and Welfarementioning

confidence: 99%

“…Double-gene-knockout (DKO) pigs containing KOs for known receptor proteins CD163 and pAPN are reported to be completely resistant to genotype 2 PRRSV and TGEV ( Xu et al, 2020 ). Additional infection challenge experiments have shown that these DKO pigs exhibit decreased susceptibility to PDCoV, thus providing in vivo evidence that pAPN as likely to be one of PDCoV receptors.…”

Section: Gene Editing Applications In Agriculturementioning

confidence: 99%

Improvements in Gene Editing Technology Boost Its Applications in Livestock

et al. 2021

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Accelerated development of novel CRISPR/Cas9-based genome editing techniques provides a feasible approach to introduce a variety of precise modifications in the mammalian genome, including introduction of multiple edits simultaneously, efficient insertion of long DNA sequences into specific targeted loci as well as performing nucleotide transitions and transversions. Thus, the CRISPR/Cas9 tool has become the method of choice for introducing genome alterations in livestock species. The list of new CRISPR/Cas9-based genome editing tools is constantly expanding. Here, we discuss the methods developed to improve efficiency and specificity of gene editing tools as well as approaches that can be employed for gene regulation, base editing, and epigenetic modifications. Additionally, advantages and disadvantages of two primary methods used for the production of gene-edited farm animals: somatic cell nuclear transfer (SCNT or cloning) and zygote manipulations will be discussed. Furthermore, we will review agricultural and biomedical applications of gene editing technology.

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

Cited by 99 publications

References 49 publications

Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control

Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control

Current status of the application of gene editing in pigs

Improvements in Gene Editing Technology Boost Its Applications in Livestock

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