The circular profiles seen in TEM were clearly demonstrated by ET to be spherical vesicles bound by a single membrane and to have pore-like connections to the cytoplasm or to other vesicles in Vero and ISE6 cells. The function of the vesicles is thought to be to minimize exposure of the replicative form dsRNA to innate immune sensors, such as RIG I [27, 58, 59] , while the pores are thought to provide a conduit for nucleotides, amino acids, and other components required for replication and gene expression [30] . In brief, our findings suggest marked similarities between acute replication in ISE6 and Vero cells, and further demonstrate the similarity between cellular features of acute tick-borne and mosquito-borne [30, 31] flavivirus replication.