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.

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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