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 (G Mok) and rabies virus (PV strain) (G PV), 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 G Mok trimer is less stable than G PV trimer. A chimeric glycoprotein (G Mok–PV) associating the N-terminal half of G Mok to the C-terminal half part of G PV 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 G Mok (and not G Mok–PV) was able to induce fusion at a higher pH (0.5 pH unit) than G PV. 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.