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Engineering of a parainfluenza virus type 5 fusion protein (PIV-5 F): Development of an autonomous and hyperfusogenic protein by a combinational mutagenesis approach

Authors
Journal
Virus Research
0168-1702
Publisher
Elsevier
Publication Date
Volume
146
Identifiers
DOI: 10.1016/j.virusres.2009.09.009
Keywords
  • Paramyxoviridae
  • Paramyxovirus
  • Parainfluenza
  • Class I Viral Glycoprotein
  • Fusion Protein
Disciplines
  • Biology
  • Engineering
  • Medicine

Abstract

Abstract The entry of enveloped viruses into host cells is accomplished by fusion of the viral envelope with the target cell membrane. For the paramyxovirus parainfluenza virus type 5 (PIV-5), this fusion involves an attachment protein (HN) and a class I viral fusion protein (F). We investigated the effect of 20 different combinations of 12 amino-acid substitutions within functional domains of the PIV-5 F glycoprotein, by performing cell surface expression measurements, quantitative fusion and syncytia assays. We found that combinations of mutations conferring an autonomous phenotype with mutations leading to an increased fusion activity were compatible and generated functional PIV-5 F proteins. The addition of mutations in the heptad-repeat domains led to both autonomous and hyperfusogenic phenotypes, despite the low cell surface expression of the corresponding mutants. Such engineering approach may prove useful not only for deciphering the fundamental mechanism behind viral-mediated membrane fusion but also in the development of potential therapeutic applications.

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