Resistance to coronavirus infection in amino peptidase N-deficient pigs

The alphacoronaviruses, transmissible gastroenteritis virus (TGEV) and Porcine epidemic diarrhea virus (PEDV) are sources of high morbidity and mortality in neonatal pigs, a consequence of dehydration caused by the infection and necrosis of enterocytes. The biological relevance of amino peptidase N...

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Bibliographic Details
Published in:Transgenic research 2019-02, Vol.28 (1), p.21-32
Main Authors: Whitworth, Kristin M., Rowland, Raymond R. R., Petrovan, Vlad, Sheahan, Maureen, Cino-Ozuna, Ada G., Fang, Ying, Hesse, Richard, Mileham, Alan, Samuel, Melissa S., Wells, Kevin D., Prather, Randall S.
Format: Article
Language:English
Subjects:
Animal Genetics and Genomics
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Coronaviridae
Coronaviruses
CRISPR
Dehydration
Diarrhea
Enterocytes
Gastroenteritis
Genetic Engineering
Ileum
Immunohistochemistry
Infections
Life Sciences
Molecular Medicine
Morbidity
Neonates
Nonsense mutation
Nucleic acids
Original Paper
Peptidase
Phenotypes
Plant Genetics and Genomics
Stop codon
Suidae
Transgenics
Transmissible gastroenteritis
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Summary:The alphacoronaviruses, transmissible gastroenteritis virus (TGEV) and Porcine epidemic diarrhea virus (PEDV) are sources of high morbidity and mortality in neonatal pigs, a consequence of dehydration caused by the infection and necrosis of enterocytes. The biological relevance of amino peptidase N (ANPEP) as a putative receptor for TGEV and PEDV in pigs was evaluated by using CRISPR/Cas9 to edit exon 2 of ANPEP resulting in a premature stop codon. Knockout pigs possessing the null ANPEP phenotype and age matched wild type pigs were challenged with either PEDV or TGEV. Fecal swabs were collected daily from each animal beginning 1 day prior to challenge with PEDV until the termination of the study. The presence of virus nucleic acid was determined by PCR. ANPEP null pigs did not support infection with TGEV, but retained susceptibility to infection with PEDV. Immunohistochemistry confirmed the presence of PEDV reactivity and absence of TGEV reactivity in the enterocytes lining the ileum in ANPEP null pigs. The different receptor requirements for TGEV and PEDV have important implications in the development of new genetic tools for the control of enteric disease in pigs.
ISSN:0962-8819
1573-9368
DOI:10.1007/s11248-018-0100-3