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

4.9 Discussion.
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Over expression of SR-BI in Huh-7.5 cells increases their susceptibility to
HCVcc (Figure 4-2), indicating that infection is limited by SR-BI expression
levels. We made similar, though less pronounced, observations using cells
over expressing the splice variant SR-BII, suggesting that it is a functionally
active receptor for HCV attachment and/or entry (Figure 4-2). Comparable
findings were reported for CD4 and chemokine receptor expression levels
influencing human immunodeficiency virus cell entry (13, 249).
Over expression of SR-BI enhanced JFH-1 infectivity to a much greater extent
than J6/JFH; 18-fold and 3-fold, respectively (Figure 4-2), suggesting strain
specific variation within genotypic clades. HCVpp expressing diverse
glycoproteins vary in their ability to infect HepG2 cells expressing CD81,
supporting a model of genotypic variants with different dependencies for the
viral co-receptors (101, 202).
HCVpp-JFH-1 infection of Huh-7.5 cells over expressing SR-BI was enhanced
2 fold indicating that the restriction occurs at the point of virus entry (Figure
4-4). However, this increase in HCVpp infection, was much less pronounced
than that seen with JFH-1 HCVcc, suggesting a disparity between the two
model systems. This discrepancy may be accounted for by the increase in
JFH-1 infected cell focus size in cells over expressing SR-BI, as foci occur
following multiple rounds of replication and HCVpp do not mimic this process.
The fact that a large proportion of JFH-1 infected Huh-7.5 TRIP SR-BI cells
reside in large foci (Figure 4-3) suggests that the phenotype seen in these