Neuroblastoma Cell Fusion by a Temperature-Sensitive Mutant of Vesicular Stomatitis Virus

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Abstract
A temperature sensitive mutant of vesicular stomatitis virus which does not mature properly when grown at 39.degree. C promoted extensive fusion of murine neuroblastoma cells at this nonpermissive temperature. Polykaryocytes apparently formed as a result of fusion from within the cells that required low doses of infectious virions for its promotion and was dependent on viral protein synthesis. Although 90% of infected N-18 neuroblastoma cells were fused by 15 h after infection, larger polykaryocytes continued to form, leading to an average of 28 nuclei per polykaryocyte as a result of polykaryocytes fusing to each other. Two neuroblastoma cell lines were observed to undergo fusion, whereas three other cell lines ([baby hamster kidney] BHK-21, [chinese hamster ovary] CHO and [mouse fibroblast] 3T3) were incapable of forming polykaryocytes, suggesting that nervous system-derived cells were particularly susceptible to vesicular stomatitis virus-induced fusion. Although the normal assembly of the protein components of this virus was deficient at 39.degree. C, the G glycoprotein was inserted into the infected cell membranes at this temperature. Two lines of evidence suggest that the expression of G at the cell surface promoted this polykaryocyte formation: inhibition of glycosylation, which may be involved in the migration of the G protein to the cellular plasma membranes, will inhibit the cell fusion reaction and addition of antiserum, directed toward the purified G glycoprotein, will also inhibit cell fusion.