FIGURE 7.

Flavivirus shares a common RC generation mechanism. (A,B) DENV and WNV NS1 possessed a similar binding pattern to negatively charged lipids as ZIKV NS1. Lipid membrane strips were used to examine the lipid-binding selectivity of DENV (A) and WNV NS1 (B). (C) Flaviviral NS1 proteins located in the ER lumen bind to the inner leaflet of the ER membrane by hydrophobic insertion, and the electrostatic interaction with negatively charged lipids (e.g., PI4P) facilitates the association between NS1 and membrane. This insertion of NS1 changes the ER membrane’s curvature, producing invaginated vesicles as the place of viral RNA synthesis, the replication compartment.