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Published on: January 9, 2019
Fusion protein is the main determinant of metapneumovirus host tropism
Miranda de Graaf1, Eefje J A Schrauwen1, Sander Herfst1
1Department of Virology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
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.
Insights
The fusion (F) protein of metapneumoviruses determines host tropism, with the AMPV-C F protein showing greater fusogenicity. This finding explains differences in HMPV and AMPV-C replication in avian cells.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Human metapneumovirus (HMPV) and avian metapneumovirus subgroup C (AMPV-C) exhibit distinct host ranges, infecting humans and birds, respectively.
- Understanding the genetic determinants of these host specificities is crucial for viral pathogenesis research.
Purpose of the Study:
- To investigate the contribution of individual metapneumovirus genes to host range.
- To identify the viral proteins responsible for differential replication in mammalian versus avian cell lines.
Main Methods:
- Utilized recombinant HMPV and AMPV-C with gene exchanges.
- Employed in vitro cell-culture models (Vero-118 mammalian cells and QT6 avian cells).
- Applied mini-genome systems to assess replication and transcription efficiency.
Main Results:
- The metapneumovirus fusion (F) protein was identified as the primary determinant of host tropism.
- Chimeric viruses with exchanged polymerase proteins showed reduced replication in avian cells.
- AMPV-C F protein promoted larger syncytia formation and exhibited higher fusogenicity, particularly the F2 region.
Conclusions:
- The F protein, specifically its F2 region, dictates metapneumovirus host tropism and membrane fusion capabilities.
- Differential fusogenicity of the F protein underlies the observed host range differences between HMPV and AMPV-C.
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