The role of scavenger receptor BI in hepatitis - eTheses Repository ...

1.4.3 Endocytosis and fusion
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After successful binding to a target cell a virion must cross a cellular
membrane to gain entry to the interior. HCV has an enveloped particle and
most likely achieves this by fusion of its own lipid membrane with that of the
host cell, allowing free passage of the capsid into the cytoplasm (150). Viral
fusion events occur either at the plasma membrane (e.g. HIV) or in an
intracellular compartment after endocytosis (e.g. Influenza) and normally
involve a conformational change in an envelope protein exposing a fusion
peptide (150, 194). These hydrophobic domains insert into the target
membrane as homotrimers, allowing the formation of a ‘hair-pin’ structure that
bring the virus and host lipid bilayers into contact, as reviewed by Kielian and
Rey (150).
The penetration of a number of viruses has been well characterised and as
such theorising over the fusion strategy employed by HCV was possible long
before an in vitro model of entry was available. For instance proteomic
analysis of HCV E1 suggests it is a class II fusion protein similar to that of
another Flavivirus, tick-borne encephalitis virus (108). Using well established
tools for investigating virus fusion, the HCVcc/pp systems are now allowing
the elucidation of HCV fusion events.
Class II fusion proteins typically initiate virion penetration after endocytosis in
acidified endosomal compartments; low pH being necessary for the exposure
of the fusion peptide (150, 195). Indeed compounds that disrupt the regulation