The accumulation of insoluble, α-synuclein (aSyn)-rich Lewy bodies within surviving nerve cells is considered a hallmark of Parkinson disease (PD). It is thought that changes in the protein's metabolism, including its aggregation and sustained phosphorylation at serine 129, are linked to PD pathogenesis. Previously, Braak et al. theorized that microbial infections could constitute environmental factors contributing to PD development. Previously, we and others have shown that wild-type aSyn confers partial protection of mice against invasion by select bacteria and RNA viruses. Here, I hypothesized that aSyn metabolism is altered in response to microbial infections and that PD-linked mutations in aSyn modify this response. Vesicular Stomatitis Virus (VSV) causes systemic infections, leading to encephalitis in rodents. In the present study, infections of neural cell lines by a GFP-expressing VSV variant were used to: 1) explore possible anti-viral properties of aSyn and identify potential differences between select aSyn mutants; and 2) monitor changes in the protein's metabolism following viral infection. When comparing the possible anti-viral effects of either wild-type aSyn or mutant proteins to a control arm, I observed trends but no significant difference using two neural cell culture models. When investigating the effects of wild-type VSV infection on the protein itself, I observed increased oligomerization of aSyn. Although these results did not substantiate an essential role for aSyn within neural cells' innate defence to VSV, they revealed that aSyn metabolism is altered following infection by VSV. These findings could inform concepts that explore the start of PD at epithelial host surfaces.