title: Fusion protein is the main determinant of metapneumovirus host tropism.
abstract: Human metapneumovirus (HMPV) and avian metapneumovirus subgroup C (AMPV-C) infect humans and birds, respectively. This study confirmed the difference in host range in turkey poults, and analysed the contribution of the individual metapneumovirus genes to host range in an in vitro cell-culture model. Mammalian Vero-118 cells supported replication of both HMPV and AMPV-C in contrast to avian quail fibroblast (QT6) cells in which only AMPV-C replicated to high titres. Inoculation of Vero-118 and QT6 cells with recombinant HMPV in which genes were exchanged with those of AMPV-C revealed that the metapneumovirus fusion (F) protein is the main determinant for host tropism. Chimeric viruses in which polymerase complex proteins were exchanged between HMPV and AMPV-C replicated less efficiently compared with HMPV in QT6 cells. Using mini-genome systems, it was shown that exchanging these polymerase proteins resulted in reduced replication and transcription efficiency in QT6 cells. Examination of infected Vero-118 and QT6 cells revealed that viruses containing the F protein of AMPV-C yielded larger syncytia compared with viruses containing the HMPV F protein. Cell-content mixing assays revealed that the F protein of AMPV-C was more fusogenic compared with the F protein of HMPV, and that the F2 region is responsible for the difference observed between AMPV-C and HMPV F-promoted fusion in QT6 and Vero-118 cells. This study provides insight into the determinants of host tropism and membrane fusion of metapneumoviruses.
authors.affiliation: Department of Virology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: de Graaf
authors.affiliation: Department of Virology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Eefje J A
authors.initials: EJA
authors.lastname: Schrauwen
authors.affiliation: Department of Virology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Herfst
authors.affiliation: Department of Virology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.affiliation: Department of Virology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: ADME
authors.lastname: Osterhaus
authors.affiliation: Department of Virology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Ron A M
authors.initials: RAM
authors.lastname: Fouchier
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D029121:Metapneumovirus / Q000502:physiology*; D011784:Quail; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000502:physiology; D011995:Recombination, Genetic; D014422:Turkeys; D014760:Viral Fusion Proteins / Q000235:genetics / Q000502:physiology*; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: D014760:Viral Fusion Proteins; D012324:RNA-Dependent RNA Polymerase