Biology Reference
In-Depth Information
involved in the specific attachment of virus to host cells and, in some
cases, in viral entry. Affinity of viral envelope proteins with a particular
receptor may generally restrict host range, tropism and pathogenicity,
although different viruses that have different or partially crossed path-
ogenicity may utilize the same receptors. Receptors need not to be
membrane proteins, as carbohydrates or lipids have been identified as
receptors for different viruses.
91
HCV E1 and E2 proteins are the viral
component thought to be present at the surface of the viral particles.
E1 and E2 proteins contain a large ectodomain region in the N-terminus
and a hydrophobic transmembrane region including retention signals
in the C-terminus, therefore these proteins are normally retained in the
ER membrane.
22
The ectodomains of E1 and E2 proteins are post-
translationally modified by extensive N-linked glycosylation.
26,31,109
E1
and E2 proteins have 5 and 11 potential glycosylation sites, respec-
tively, and then these glycans play an important role in the folding of
E1 and E2 proteins.
38
Several molecules including human CD81
(hCD81),
80
low-density lipoprotein receptor (LDLr),
2
scavenger
receptor class B type I (SR-BI),
88
dendritic cell-specific intracellular
adhesion molecule 3-grabbing nonintegrin (DC-SIGN)/liver and
lymphnode-specific intracellular adhesion molecule 3-grabbing nonin-
tegrin (L-SIGN),
34
asialoglycoprotein receptor,
87
have been identified
to be candidates for a receptor or co-receptor for viral entry. However,
the final determination of receptor or co-receptor requirements for
HCV is difficult because of the lack of a reliable cell culture systems
and a sufficient amount of native viral particles. Three surrogate sys-
tems have been developed to study the initial step of HCV infection
(Fig. 2). Soluble truncated E2 protein,
30,59,80,81,88
liposomes reconsti-
tuted with E1 and E2 proteins,
51
HCV-like particles (HCV-LPs)
106,112
expressed in insect cells and authentic HCV particles in sera of patients
have been used to study to identify binding receptors molecules. Cell
fusion assay
98
was established to examine the membrane fusion activity
of HCV envelope proteins after modifying the original method.
28
Pseudotype virus systems based on vesicular stomatitis virus
(VSV),
50,66
influenza virus,
29
retroviruses,
9
and lentivirus
44
have also
been established to identify entry receptors for HCV.
