title: Nipah virus fusion protein: Importance of the cytoplasmic tail for endosomal trafficking and bioactivity.
abstract: Nipah virus (NiV) is a highly pathogenic paramyxovirus which encodes two surface glycoproteins: the receptor-binding protein G and the fusion protein F. As for all paramyxoviruses, proteolytic activation of the NiV-F protein is an indispensable prerequisite for viral infectivity. Interestingly, proteolytic activation of NiV-F differs principally from other paramyxoviruses with respect to protease usage (cathepsins instead of trypsin- or furin-like proteases), and the subcellular localization where cleavage takes place (endosomes instead of Golgi or plasma membrane). To allow efficient F protein activation needed for productive virus replication and cell-to-cell fusion, the NiV-F cytoplasmic tail contains a classical tyrosine-based endocytosis signal (Y525RSL) that we have shown earlier to be needed for F uptake and proteolytic activation. In this report, we furthermore revealed that an intact endocytosis signal alone is not sufficient for full bioactivity. The very C-terminus of the cytoplasmic tail is needed in addition. Deletions of more than four residues did not affect F uptake or endosomal cleavage but downregulated the surface expression, likely by delaying the intracellular trafficking through endosomal-recycling compartments. Given that the NiV-F cytoplasmic tail is needed for timely and correct intracellular trafficking, endosomal cleavage and fusion activity, the influence of tail truncations on NiV-mediated cell-to-cell fusion and on pseudotyping lentiviral vectors is discussed.
authors.affiliation: Institute of Virology, Philipps University of Marburg, Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
authors.affiliation: Institute of Virology, Philipps University of Marburg, Marburg, Germany. Electronic address: maisner@staff.uni-marburg.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maisner
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D002459:Cell Fusion; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004285:Dogs; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D004789:Enzyme Activation; D061985:Madin Darby Canine Kidney Cells; D045405:Nipah Virus / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D059748:Proteolysis; D015398:Signal Transduction; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: C510755:F protein, Nipah virus; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D002403:Cathepsins
keywords: Cleavage; Cytoplasmic tail; Endocytosis; Fusion activity; Fusion protein; Nipah virus