title: Rafts promote assembly and atypical targeting of a nonenveloped virus, rotavirus, in Caco-2 cells.
abstract: Rotavirus follows an atypical pathway to the apical membrane of intestinal cells that bypasses the Golgi. The involvement of rafts in this process was explored here. VP4 is the most peripheral protein of the triple-layered structure of this nonenveloped virus. High proportions of VP4 associated with rafts within the cell as early as 3 h postinfection. In the meantime a significant part of VP4 was targeted to the Triton X-100-resistant microdomains of the apical membrane, suggesting that this protein possesses an autonomous signal for its targeting. At a later stage the other structural rotavirus proteins were also found in rafts within the cells together with NSP4, a nonstructural protein required for the final stage of virus assembly. Rafts purified from infected cells were shown to contain infectious particles. Finally purified VP4 and mature virus were shown to interact with cholesterol- and sphingolipid-enriched model lipid membranes that changed their phase preference from inverted hexagonal to lamellar structures. Together these results indicate that a direct interaction of VP4 with rafts promotes assembly and atypical targeting of rotavirus in intestinal cells.
authors.affiliation: INSERM U 538, CHU Saint Antoine, Université Pierre et Marie Curie, 75012 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sapin
authors.forename: Odile
authors.initials: O
authors.lastname: Colard
authors.forename: Olivier
authors.initials: O
authors.lastname: Delmas
authors.forename: Cedric
authors.initials: C
authors.lastname: Tessier
authors.forename: Michelyne
authors.initials: M
authors.lastname: Breton
authors.forename: Vincent
authors.initials: V
authors.lastname: Enouf
authors.forename: Serge
authors.initials: S
authors.lastname: Chwetzoff
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Ouanich
authors.forename: Jean
authors.initials: J
authors.lastname: Cohen
authors.forename: Claude
authors.initials: C
authors.lastname: Wolf
authors.forename: Germain
authors.initials: G
authors.lastname: Trugnan
mesh_terms: D018938:Caco-2 Cells / Q000821:virology*; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D002462:Cell Membrane / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D012401:Rotavirus / Q000378:metabolism / Q000472:pathogenicity*; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins; C060339:VP4 protein, Rotavirus; D017830:Octoxynol