title: Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation.
abstract: Canine distemper virus (CDV) was shown to use dog nectin-4 as a receptor to gain entry into epithelial cells. RNA from dog placenta or MDCK kidney cells was isolated and cDNAs were prepared. Two splice variants of dog nectin-4 were identified. A deletion of 25 amino acids was found in the cytoplasmic domain of dog nectin-4 from MDCK cells, corresponding to a splice variant that is also seen in murine nectin-4, and did not affect its role as a receptor. Both dog nectin-4 and human nectin-4 could function as an entry factor for CDV containing an EGFP reporter gene. Inhibition of dog nectin-4 expression by RNAi or nectin-4 antibodies decreased CDV titers and EGFP fluorescence. Finally, dog nectin-4 also promotes syncytia formation, which could be inhibited by siRNA treatment. These data confirm that dog nectin-4 can be used by CDV to gain entry into epithelial cells, and facilitate virus spread.
authors.affiliation: The Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada B3H 1X5.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Noyce
authors.forename: Sebastien
authors.initials: S
authors.lastname: Delpeut
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Richardson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004217:Distemper Virus, Canine / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D015726:Giant Cells / Q000378:metabolism* / Q000821:virology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D000075983:Nectins; D010920:Placenta; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D017384:Sequence Deletion; D014709:Vero Cells; D053586:Virus Internalization
chemical_list: D000906:Antibodies; D015815:Cell Adhesion Molecules; D000075983:Nectins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins