title: The CD46 transmembrane domain is required for efficient formation of measles-virus-mediated syncytium.
abstract: Two phosphatidylinositol (PI)-anchored versions of a measles virus (MV) receptor membrane cofactor protein (MCP; CD46) were generated by fusing the extracellular domain of MCP to the decay-accelerating factor (DAF; CD55) or its PI anchor. The PI-anchored forms of MCP expressed on Chinese hamster ovary cells, otherwise non-permissive to MV, conferred a smaller MV cytopathic effect than a wild-type MCP, a Ser/Thr-rich domain-deletion mutant and a cytoplasmic tail-deletion mutant of MCP. Therefore the differences in MV receptor properties between the two PI-anchored and three transmembrane forms were investigated. The PI-anchored forms were predominantly expressed on microvilli as in DAF, whereas the other transmembrane forms were found on intracellular membranes. The PI-anchored forms conferred high MV-binding capacity compared with the transmembrane versions. MV replication was, however, severely suppressed in cells expressing the PI-anchored forms, resulting in ineffective syncytium formation. In contrast, cell-to-cell fusion occurred efficiently after co-transfection of cDNA species encoding MV-H. MV-F and any version of MCP. Thus the PI-anchored forms, despite showing sufficient MV binding and cell-to-cell fusion competence together with MV-H and MV-F, mediate inefficient MV entry or replication, which causes severe suppression of the MV cytopathic effect. A biased receptor distribution on microvilli might participate in the selection of a low MV uptake pathway in the PI-anchored forms of MCP. Taken together, the transmembrane portion of MCP is a critical factor for effective virus-cell fusion and the subsequent MV replication.
authors.affiliation: Department of Immunology, Center for Adult Diseases Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Seya
authors.forename: M
authors.initials: M
authors.lastname: Kurita
authors.forename: K
authors.initials: K
authors.lastname: Iwata
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagi
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Shida
authors.forename: M
authors.initials: M
authors.lastname: Hatanaka
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Jun
authors.forename: A
authors.initials: A
authors.lastname: Hirano
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Nagasawa
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D015726:Giant Cells / Q000276:immunology* / Q000502:physiology / Q000821:virology*; D008459:Measles virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010716:Phosphatidylinositols