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. 2021 Mar 22;13(3):520. doi: 10.3390/v13030520

Figure 2.

Figure 2

One proposed model for the formation of HCV replication organelles (RO). Double-membrane vesicles (DMV) biogenesis is a complex process possibly requiring several membrane remodeling steps, including budding, fission, pairing, curvature, and fusion [11,17]. HCV DMV formation can be induced by NS5A with the help of other nonstructural proteins [25,26]. HCV activates the lipid kinase PI4KIIIα to generate enhanced levels of PI4P, which in turn attracts lipid transport proteins (e.g., OSBP, FAPP2, NPC1 and CERT) delivering cholesterol and glycosphingolipids into DMVs. PSTPIP2, a protein with membrane-deforming activity, and PLA2G4C are also critical for membrane web (MW) formation. HCV RNA replication can be conducted by NS5B with the help of other nonstructural proteins in the closed DMVs. After the completion of HCV genomic RNA synthesis, the newly synthesized viral RNAs will be released from the open DMVs (possibly with Kaps or Nups) for translation or virion assembly. Other possible models for DMV formation have also been proposed [11].