Biology Reference
In-Depth Information
3)
LDLr
HCV has an unusually low buoyant density in plasma due to an asso-
ciation with various forms of lipoprotein, in particular LDL.
64,71,82
Several groups have recently been reported that LDLr is a cell surface
molecule mediating attachment and endocytosis of HCV associated
with very-low-density lipoprotein (VLDL) or LDL in serum.
2,5,72
In
contrast, HCV purified from plasma fractions without VLDL or LDL
did not exhibit measurable LDLr-mediated binding or endocytosis.
Apolipoprotein B and apolipoprotein E integrated in LDL or VLDL
are essential for binding to the LDLr, because antibody against
apolipoprotein B or apolipoprotein E could inhibit the interaction
between HCV and LDLr.
2
Interestingly, the interaction between HCV
particles from patient plasma and the LDLr was not correlated to the
interaction of HCV E2 protein with LDLr.
114
The binding of HCV
particles in LDL fractions from patient serum to MOLT-4 cells was
higher than those in intermediate-density lipoprotein (IDL) fractions.
This binding was correlated with LDLr expression and inhibited by
LDL but not soluble hCD81, whereas the binding of E2 protein to
MOLT-4 cells was not inhibited by LDL but soluble hCD81 is com-
pletely inhibited.
114
Another group was also demonstrated that HCV
RNA-containing particles were mostly presented in the LDL fractions
among the fractions of VLDL, IDL, and LDL. Binding of these parti-
cles was also inhibited by VLDL and LDL or anti-apolipoprotein B
and E antibodies, whereas their internalization were increased by the
upregulation of LDLr.
5
In contrast, HCV-LPs exhibited binding to
human hepatoma and lymphoma cell lines in dose-dependent and sat-
urable manner, but did not correlate with LDLr expression. Although
LDLr expression was upregulated in MOLT-4 cells cultured under the
lipoprotein-deficient condition, HCV-LPs binding was markedly
decreased, suggesting that HCV-LPs bind to hepatoma or lymphoma
cell lines independently of LDLr expression.
106,112
In addition, infection of pseudotype MLVs was not inhibited by
VLDL and LDL on Huh7 cells which express LDLr.
9
On the other
hand, pseudotype VSVs possessing chimeric E1 protein alone were
partially inhibited by excess amount of LDL, suggesting the interaction
