Resistance to coronavirus infection in amino peptidase N-deficient pigs

Whitworth, Kristin M.; Rowland, Raymond R. R.; Petrovan, Vlad; Sheahan, Maureen A.; Cino‐Ozuna, Ada G.; Fāng, Yīng; Hesse, Richard; Mileham, Alan J.; Samuel, Melissa; Wells, Kevin D.; Prather, Randall S.

doi:10.1007/s11248-018-0100-3

Cited by 99 publications

(83 citation statements)

References 45 publications

(59 reference statements)

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“…Researchers from the Roslin Institute have proposed to edit the domestic pig inducing this variation in RELA with the aim to confer disease resilience to this virus [55,56]. In another study, CRISPR has also been used to produce Coronavirus resistant pigs, by editing a putative receptor of the transmissible gastroenteritis virus [57]. In China, edited cows with increased resistance to tuberculosis were produced through CRISPR [10].…”

Section: Stage Of Embryosmentioning

confidence: 99%

CRISPR in livestock: From editing to printing

et al. 2020

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a b s t r a c tPrecise genome editing of large animals applied to livestock and biomedicine is nowadays possible since the CRISPR revolution. This review summarizes the latest advances and the main technical issues that determine the success of this technology. The pathway from editing to printing, from engineering the genome to achieving the desired animals, does not always imply an easy, fast and safe journey. When applied in large animals, CRISPR involves time-and cost-consuming projects, and it is mandatory not only to choose the best approach for genome editing, but also for embryo production, zygote microinjection or electroporation, cryopreservation and embryo transfer. The main technical refinements and most frequent questions to improve this disruptive biotechnology in large animals are presented. In addition, we discuss some CRISPR applications to enhance livestock production in the context of a growing global demand of food, in terms of increasing efficiency, reducing the impact of farming on the environment, enhancing pest control, animal welfare and health. The challenge is no longer technical. Controversies and consensus, opportunities and threats, benefits and risks, ethics and science should be reconsidered to enter into the CRISPR era.

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Section: Stage Of Embryosmentioning

confidence: 99%

CRISPR in livestock: From editing to printing

et al. 2020

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“…Previous work from our lab showed that ANPEP KO pigs are completely resistant to infection with TGEV (Whitworth et al, 2018). We tested the ability of PDCoV to infect ANPEP KO pigs.…”

Section: Pdcov Infection Of Anpep Wt and Ko Pigsmentioning

confidence: 99%

The use of cells from ANPEP knockout pigs to evaluate the role of aminopeptidase N (APN) as a receptor for porcine deltacoronavirus (PDCoV)

Stoian¹,

Rowland²,

Petrovan³

et al. 2020

Virology

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A B S T R A C TThe coronaviruses, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine deltacoronavirus (PDCoV) represent important sources of neonatal diarrhea on pig farms. The requirement for aminopeptidase N (APN) as a receptor for TGEV, but not for PEDV, is well established. In this study, the biological relevance of APN as a receptor for PDCoV was tested by using CRISPR/Cas9 to knockout the APN gene, ANPEP, in pigs. Porcine alveolar macrophages (PAMs) from ANPEP knockout (KO) pigs showed resistance to PDCoV infection. However, lung fibroblast-like cells, derived from the ANPEP KO PAM cultures, supported PDCoV infection to high levels. The results suggest that APN is a receptor for PDCoV in PAMs but is not necessary for infection of lung-derived fibroblast cells. The infection of the ANPEP KO pigs with PDCoV further confirmed that APN is dispensable as a receptor for PDCoV.

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“…The use of genome editing to generate pigs lacking aminopeptidase N successfully showed that pigs resistant to TGEV infection could be generated. However, the edited animals remained susceptible to PEDV infection (Whitworth et al, 2019). Aminopeptidase N is important for peptide digestion in the small intestine and knockout mice were shown to have delayed mammary gland development.…”

Section: Pigsmentioning

confidence: 99%