Vector-borne flaviviruses replicate in both mammalian and arthropod cells. However, the three-dimensional (3D) fine structure of TBFV replication in mammalian cells has not yet been compared to that in acutely or persistently infected tick cells. In order to undertake this comparison, baseline characterizations of acutely infected mammalian (African green monkey kidney, Vero) and tick (Ixodes scapularis embryo derived, ISE6) cells were performed by light microscopy and virus titer was assayed from culture supernatants. Uninfected Vero cell cultures formed a monolayer of uniform elongated, fibroblast-like cells that were firmly adherent to the culture vessel. Infected Vero cells first showed cytopathic effect (CPE) by 24 hpi, consisting of rounded cells and syncytia (Fig. 1A) . The CPE was progressive and by 96 hpi, Vero cells showed extensive evidence of cell death (shape irregularity, cytoplasmic condensation, blebbing, and an inability to exclude trypan blue). After 96 hours, very few cells remained attached to the culture vessel.