Considering the central role of endothelial cells as the structural and functional core of the BBB, and the limited understanding of how IFN responses and viral replication affect these cells relative to other systems, here, we compared the infection dynamics of ZIKVMR766 and ZIKVPE243 in HBMECs, aiming to identify molecular differences that could explain the distinct virulence profiles previously observed. The gene discussed is IFNA1; the disease is infection.