title: Differential stability and fusion activity of Lyssavirus glycoprotein trimers.
abstract: The oligomeric structure and the fusion activity of lyssavirus glycoprotein (G) was studied by comparing G from Mokola virus (GMok) and rabies virus (PV strain) (GPV), which are highly divergent lyssaviruses. G expressed at the surface of BSR cells upon either plasmid transfection or virus infection are shown to be mainly trimeric after cross-linking experiments. However, solubilization by a detergent (CHAPS) and analysis in sucrose sedimentation gradient evidenced that GMok trimer is less stable than GPV trimer. A chimeric glycoprotein (G Mok-PV) associating the N-terminal half of GMok to the C-terminal half part of GPV formed trimers with an intermediate stability, indicating that the G C-terminal domain is essential in trimer stability. A cell to cell fusion assay revealed that GMok (and not G Mok-PV) was able to induce fusion at a higher pH (0.5 pH unit) than GPV. Such differences in the oligomeric structure stability and in the fusion activity of lyssavirus glycoproteins may partly account for the previously reported differences of their immunogenic and pathogenic properties.
authors.affiliation: Laboratoire des Lyssavirus, Département de Virologie, Institut Pasteur, 28 rue du Dr Roux, 75724 Cedex 15, Paris, France. pperrin@pasteur.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Desmézières
authors.forename: Antoine P
authors.initials: AP
authors.lastname: Maillard
authors.forename: Yves
authors.initials: Y
authors.lastname: Gaudin
authors.forename: Noël
authors.initials: N
authors.lastname: Tordo
authors.forename: Pierre
authors.initials: P
authors.lastname: Perrin
mesh_terms: D000818:Animals; D000956:Antigens, Viral; D002459:Cell Fusion; D002460:Cell Line; D006224:Cricetinae; D019281:Dimerization; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D018114:Lyssavirus / Q000378:metabolism / Q000472:pathogenicity*; D008561:Membrane Fusion; D011820:Rabies virus / Q000378:metabolism / Q000472:pathogenicity*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus