Biology Reference
In-Depth Information
sulfate and then transferred to a cell surface receptor and/or co-receptor,
and internalized into cells through endocytosis. After uncoating, viral
RNA is translated into a precursor polyprotein that is processed into
each viral protein by cellular and viral proteases. Viral replication uti-
lizes the viral polymerase complex and takes place on the ER mem-
brane. Core protein was shown to directly bind to the viral sense
RNA, 95 and it was suggested to form the nucleocapsid. HCV particles
seem to bud into the ER lumen after interaction of the nucleocapsid
with E1 and E2 proteins. The small hydrophobic peptide p7 was sug-
gested to form an ion channel, 16,39,77 based on the observation that p7
of pestivirus was shown to be essential for virus budding. 41 NS2 is a
component of the NS2-NS3 metalloprotease that autocatalyses cleav-
age of the NS2-NS3 junction. NS3 contributes to the NS2-NS3 pro-
tease and contains a separate serine protease that acts with co-factor
NS4A to release the remaining NS proteins. NS3 also contains an
RNA helicase and nucleotide triphosphatase activity required for viral
replication. NS5A was found to be a highly phosphorylated poly-
peptide that may be involved in resistance to the antiviral effects of
interferon (IFN) alpha. 62,99 NS5A plays an important role in viral
replication, because mutation of the phosphorylation sites of NS5A
resulted in the enhancement of replication in the HCV replicon cell
lines. 62 NS5B has an activity of the RNA dependent RNA polymerase
and forms replication complex with other NS proteins and host cellu-
lar proteins. 89
Advances in the treatment of chronic hepatitis C, antiviral agents
and their targets were recently described in a review by Walker and
colleagues. 111 Here, we will focussed on our knowledge on the mech-
anisms of HCV infection by using surrogate systems.
Initial Stage of HCV Infection
Host cell surface molecules required for virus entry are classified as either
receptor or co-receptor. Several viruses utilize one molecule as a recep-
tor for entry into host cells, while many viruses require co-receptor
that localize near the receptor for their entry. Receptors are primarily
Search WWH ::




Custom Search