Syncytia formation in melanoma cells infected with varicella zoster virus and the hyperfusogenic mutant gB[Y881F]
- The highly conserved herpesvirus glycoprotein complex, gB/gH-gL, mediates membrane fusion during virion entry and cell-cell fusion. Varicella-zoster virus (VZV) characteristically forms multi-nucleated fused cells, or syncytia, in cultured cells, and during infection of human host tissues but little is known about this process. The cytoplasmic domain of VZV gB has been implicated in cell fusion because substituting the tyrosine at amino acid 881 with phenylalanine (Y881F) resulted in a hyperfusogenic mutant. The importance of gB-mediated regulation of cell fusion for VZV pathogenesis was evident from the severe attenuation of this gB[Y881F] mutant in human skin xenografts in the SCID mouse model. Here VZV-induced cell fusion was investigated by comparing the properties of melanoma cells infected with the wild type pOka virus and the gB[Y881F] mutant Live cell confocal microscopy of melanoma cells (MeWo) infected with the gB[Y881F] mutant exhibited dramatically accelerated fusion, creating large syncytia, and rapid displacement of cell nuclei to dense central structures when compared to pOka. The surfaces of cells infected with the gB[Y881F] mutant also had extensive filopodia and virion assembly was severely impaired, as shown by electron microscopy.
|Type of resource
|April 10, 2013 - November 15, 2013
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