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

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5-1), better able to engage CD81 (Figure 5-2Figure 5-3Figure 5-4) and is
highly susceptible to polyclonal neutralising IgG (Figure 5-7) suggesting an
alteration in the conformation of E2.
Such a hypothesis is not unprecedented, primary attachment of HIV to CD4 +
lymphoid cells promotes a conformational change in the viral envelope
protein, gp120, which exposes epitopes that are critical for later stages of
entry (273, 315, 335). As a result, CD4 expression levels limit HIV entry and
cell culture adaptation leads to viruses with reduced dependence on CD4 and
a heightened sensitivity to nAbs (13, 38, 86, 129, 249). Similar observations
have been made using mutant respiratory syncytial virus (196). Over
expression of SR-BI enhanced JFH-1 infection to greater extent than J6/JFH,
suggesting strain specific differences in SR-BI dependency. Given our
findings using JFH-1 G451R it will be interesting to investigate how this
phenotype correlates with particle CD81 engagement and sensitivity to
neutralising antibodies.
HDL (high density lipoprotein) enhances HCVcc infection, this process is
thought to involve SR-BI mediated cholesterol exchange, followed by the
liberation of apoC-I from HDL (25, 79, 324, 325). Recent reports suggest that
apoC-I integrates into HCV particles and enhances attachment and fusion
events (79, 210, 211). Notably, JFH-1 G451R did not respond to supplemental
HDL (Figure 5-1), this is most likely linked to its lower dependence on SR-BI.
Based on our current understanding, it is difficult to speculate on the
mechanisms by which apoC-I promotes infection, however our data suggests