title: Porcine aminopeptidase N is not a cellular receptor of porcine epidemic diarrhea virus, but promotes its infectivity via aminopeptidase activity.
abstract: Porcine epidemic diarrhea virus (PEDV), a causative agent of pig diarrhoea, has recently caused significant economic damage worldwide. Porcine aminopeptidase N (pAPN) has been reported to be the receptor for PEDV, although robust evidence is lacking. In the present study, we explored whether pAPN functions as a receptor for PEDV. Human HeLa cells expressing pAPN and pAPN-positive porcine CPK cells failed to support PEDV infection, but were susceptible to infection by transmissible gastroenteritis virus (TGEV), which utilizes pAPN as a functional receptor. In contrast to TGEV, PEDV did not bind soluble porcine aminopeptidases (pAPs) and infection was not inhibited by the soluble form of pAPs. However, overexpression of pAPN in porcine CPK cells (CPK-pAPN cells) slightly increased the production of PEDV, and the increased replication in CPK-pAPN cells was inhibited by bestatin, an inhibitor of the protease activity of aminopeptidase N. These results suggest that pAPN is not a functional receptor for PEDV, but promotes the infection of PEDV through its protease activity.
authors.affiliation: Laboratory of Acute Respiratory Viral Diseases and Cytokines, Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shirato
authors.affiliation: Laboratory of Acute Respiratory Viral Diseases and Cytokines, Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Maejima
authors.affiliation: Laboratory of Virology and Viral Infections, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Md Taimur
authors.initials: MT
authors.lastname: Islam
authors.affiliation: Viral Diseases and Epidemiology Research Division, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Laboratory of Acute Respiratory Viral Diseases and Cytokines, Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kawase
authors.affiliation: Laboratory of Acute Respiratory Viral Diseases and Cytokines, Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Shutoku
authors.initials: S
authors.lastname: Matsuyama
authors.affiliation: Laboratory of Virology and Viral Infections, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino, Tokyo 180-8602, Japan.|Laboratory of Acute Respiratory Viral Diseases and Cytokines, Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D018352:Coronavirus Infections / Q000201:enzymology / Q000235:genetics / Q000662:veterinary* / Q000821:virology; D053485:Porcine epidemic diarrhea virus / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D013553:Swine Diseases / Q000201:enzymology* / Q000235:genetics / Q000821:virology
chemical_list: D011991:Receptors, Virus; D018826:CD13 Antigens