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internalization into the cell by endocytosis. Recent attempts to iden-
tify the HCV receptor revealed that several cell surface molecules
exhibit binding to HCV envelope proteins as described below.
The putative life cycle of HCV is shown in Fig. 1. At first, HCV
particles are trapped by glycosaminoglycans such as heparin or heparan
Fig. 1. Putative life cycle of HCV. HCV particles are trapped by gly-
cosaminoglycans (GAGs) on the cell surface, transferred to cell surface receptor
and/or co-receptor, and then internalized into cells through endocytosis.
hCD81, SR-B1, LDLr, DC-SIGN, and L-SIGN are identified as candidates for
HCV receptors. Acidification leads to conformational changes of the HCV
envelope proteins into a fusion competent state and induces the fusion of viral
membranes with host membranes. Fusion allows the viral genome to be liber-
ated into cytosol. After uncoating, viral RNA is translated into a precursor
polyprotein that is processed into each viral protein by cellular and viral pro-
teases, and replication takes place by the viral polymerase complex on the ER
membrane. HCV particles seem to bud into the ER lumen after assembly of the
nucleocapsid with E1 and E2 proteins and to release from the plasma mem-
brane through the secretory pathway.
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