Control of apoptosis by matrix protein of vesicular stomatitis virus

The goal of my project was to determine the role of the M protein in apoptosis induced by VSV. I have determined that M protein induces apoptosis in the absence of other viral components. The induction of apoptosis by M protein is genetically correlated with its ability to inhibit host gene expression, and there are similarities between apoptosis induced by M protein and apoptosis induced by pharmacologic inhibitors of host gene expression. Both M protein and pharmacologic inhibitors of host gene expression initially activate the mitochondrial pathway, and the receptor-mediated pathway is activated by cross-talk. I also determined that the induction of cell death pathways downstream of Bcl-2 is not required for the inhibition of host gene expression, but the induction of cell death is required for cell rounding by M protein. These results support a cause-and-effect relationship among the effects of M protein in which the inhibition of host gene expression causes the induction of apoptosis, which causes the induction of cell rounding.; I also analyzed the role of M protein in the context of a viral infection by utilizing a recombinant virus which contained an M protein that was defective in the inhibition of host gene expression. I determined that M protein and another viral component contribute to the induction of apoptosis by VSV. The effect of the inhibition of host gene expression by M protein in the context of a viral infection differs depending on the cell type. The inhibition of host gene expression by M protein accelerates apoptosis induced by VSV in HeLa cells but delays apoptosis induced by VSV in BHK cells. This is supported by the result that wildtype M protein and pharmacologic inhibitors of host gene expression have similar effects on the induction of apoptosis in both HeLa and BHK cells infected with VSV. These results support a model for induction of apoptosis by VSV in which two viral products contribute to apoptosis. Thus, my project has contributed a context for understanding of the mechanisms by which VSV causes a key step in viral pathogenesis, the induction of apoptosis.