title: Canine distemper virus with the intact C protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor.
abstract: Recent outbreaks in monkeys have proven that canine distemper virus (CDV) causes diseases in a wide range of mammals. CDV uses SLAM and nectin4 as receptors to replicate in susceptible animals. Here, we show that human nectin4, but not human SLAM, is fully functional as a CDV receptor. The CDV Ac96I strain hardly replicated in nectin4-expressing human epithelial NCI-H358 cells, but readily adapted to grow in them. Unsurprisingly, no amino acid change in the H protein was required for the adaptation. The original Ac96I strain possessed a truncated C protein, and a subpopulation possessing the intact C protein was selected after growth in NCI-H358 cells. Other CDV strains possessing the intact C protein showed significantly higher growth abilities in NCI-H358 cells than the Ac96I strain with the truncated C protein. These findings suggest that the C protein is functional in human epithelial cells and critical for CDV replication in them.
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan. otsuki@nih.go.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sekizuka
authors.forename: Fumio
authors.initials: F
authors.lastname: Seki
authors.forename: Kouji
authors.initials: K
authors.lastname: Sakai
authors.forename: Toru
authors.initials: T
authors.lastname: Kubota
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: Surui
authors.initials: S
authors.lastname: Chen
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004216:Distemper / Q000821:virology; D004217:Distemper Virus, Canine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014709:Vero Cells; D014779:Virus Replication; D000075983:Nectins
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C442228:NECTIN4 protein, human; D000075983:Nectins