The life cycle of HCV, including attachment, entry, uncoating, encapsidation and
secretion, is depicted. Interaction of extracellular HCV with cellular surface
receptors initiates the entry process, which can also occur from direct
cell-to-cell transmission. After pH-dependent fusion and uncoating, the incoming
HCV genome is translated and the resulting polyprotein processed. Replication
takes place in ER-derived membrane spherules (membranous web). In the assembly
and secretion release process, the core protein is transferred from the lipid
droplets to form nucleocapsids that, assisted by NS5A, are loaded with RNA. The
replicase proteins can bind to the HCV genomic RNA during transfer from
replication to packaging in close proximity, but eventually are removed from the
maturing nucleocapsids, the intracellular sites of which might converge. HCV
virion morphogenesis is coupled to the VLDL pathway, and particles are produced
as lipoviral particles (LVPs). CLDN1, claudin-1; cLD, cytoplasmic lipid
droplets; ER, endoplasmic reticulum; LD, lipid droplets; NPC1L1, Niemann-Pick
C1-like protein 1; OCLN, occludin; SR-B1, scavenger receptor class B member 1.
Adapted with permission from Nature Publishing Group © Scheel, T. K. H.
& Rice, C. M. Nat. Med,
19, 837–849 (2013).