Vector-borne flaviviruses, like DENV, JEV, and TBEV, must replicate in both mammalian and arthropod cells, and a limited number of comparative studies have been published [32] [33] [34] [35] [36] . The findings, generally, show agreement between mammalian and arthropod cells in virus induced structures, such as cytoplasmic membrane proliferation and vesicle formation. Some changes were noted via TEM by Senigl et al. [35] four to seven days post TBEV infection; viral particles were observed inside rough ER in mammalian cells but were visualized within vacuoles or within the cytosol in tick cells. Consequently, we have undertaken a direct comparison of LGTV infection in both mammalian and arthropod cells, and extended the results to include 3D reconstructions. In addition, we have shown for the first time the 3D structure of acute and persistent flavivirus infection in an arthropod cell line.