Hepatitis C virus: Morphogenesis, infection and therapy

Figure 5 Schematic representation of the hepatitis C virus life cycle. (1) The lipoviral particles (LVP) binds to entry factors and receptors on the surface of hepatocyte; (2) The virus enters into the cell by a clathrin-mediated endocytosis; (3) Transportation of the virus in endosome; (3) Acidification of endosome, un-coating of the virion and dissociation of the viral core; (4) Release of the viral RNA; (5 and 6) Translation and replication of the viral RNA in the ER in the convoluted membrane structure called the membranous web (shown in dark green); (7) Cleavage of the protein precursor by cellular and viral proteases, assembly of the core on the surface of the lipid droplet (LD) and recruitment of the newly synthesized viral RNA to the viral core during the formation. The mechanism of the viral RNA recruitment to the site of the assembly is not known. It is also unclear whether the core maturation is finalized at this stage; (8) The viral nucleocapsid egresses into the lumen side of the ER, likely interacted with very low-density lipoproteins (VLDL) and translocated to Golgi. It is not clear if some VLDL-free particles can also be produced (?). Details of traffic machinery are not well defined; (9) Final maturation of viruses in Golgi and virus induced partial fragmentation of Golgi; (10) The hepatitis C virus (HCV) complex with VLDL is directed to the plasma membrane using the VLDL secretory pathway; (11) Release of particles from the cell (adapted from Ref.[16,19,135]); and (12) The HCV release in MV cannot be excluded as another pathway for the virus release during active replication.