FIG 12.

Proposed model for the role of FAPP2 in HCV genome replication. (A) After translation and processing on endoplasmic reticulum (ER) membranes, HCV NS5A activates PI4KIIIα to produce PI4P. (B) FAPP2 brings glycosphingolipids (GSLs) into the HCV RC in part via interaction with PI4P. GSLs and the FAPP2 PH domain regulate ER membrane curvature to form the MW vesicles. Alternatively, GSLs control the size of the MW vesicles or the local concentration of the replicase proteins. (C) Schematic of the double-membrane vesicles, as depicted by Paul et al. (79); these vesicles are clustered into an MW structure.