Resistance to coronavirus infection in amino peptidase N-deficient pigs

• DOI: 10.1007/s11248-018-0100-3
• Publication Date: 2018-10-12T09:11:13Z
• Authors: Kristin M. Whitworth; Raymond R. R. Row...; Vlad Petrovan; Maureen Sheahan; Ada G. Cino-Ozuna; Ying Fang; Richard Hesse; Alan Mileham; Melissa S. Samuel; Kevin D. Wells; Randall S. Prather
• Keywords: Coronavirus; Nidovirales; Coronaviridae

The alphacoronaviruses, transmissible gastroenteritis virus (TGEV) and Porcine epidemic diarrhea (PEDV) are sources of high morbidity mortality in neonatal pigs, a consequence dehydration caused by the infection necrosis enterocytes. biological relevance amino peptidase N (ANPEP) as putative receptor for TGEV PEDV pigs was evaluated using CRISPR/Cas9 to edit exon 2 ANPEP resulting premature stop codon. Knockout possessing null phenotype age matched wild type were challenged with either or TGEV. Fecal swabs collected daily from each animal beginning 1 day prior challenge until termination study. presence nucleic acid determined PCR. did not support TGEV, but retained susceptibility PEDV. Immunohistochemistry confirmed reactivity absence enterocytes lining ileum pigs. different requirements have important implications development new genetic tools control enteric disease