Because viral DNA replication and/or late gene synthesis were important for endothelial cell outcome of cHV68 infection (Fig. 2B and Fig. 6A ), our findings indicate that an active viral process occurred within the cells to yield these changes. Consistent with this hypothesis, we identified that the cHV68 v-cyclin is required for optimal endothelial cell viability after cHV68 infection in vitro. The cHV68 v-cyclin promotes cell cycle progression in primary lymphocytes and can function as an oncogene in transgenic mice [18] . While the v-cyclin is critical for reactivation from latency, to date the v-cyclin has been dispensable in all assays of lytic replication in vitro [53, 54] . Given the lytic nature of endothelial cell infection, the contribution of the v-cyclin to optimal endothelial cell viability after cHV68 infection indicates a role for the v-cyclin outside of its requirement in reactivation from latency. Additionally, the apparent role of the v-cyclin in this prolonged infection of both endothelial cell lines and primary lung endothelial cells may explain the slight decrease in lung titers that resulted in mice infected with low doses of v-cyclin.STOP cHV68 and other vcyclin mutant viruses compared to wildtype cHV68 [55] . Although the precise mechanism by which the v-cyclin promotes endothelial cell viability is unknown at this time, it is possible that the v-cyclin provides growth cues that allow for anchorageindependent growth of endothelial cells after cHV68 infection.