The role of scavenger receptor BI in hepatitis - eTheses Repository ...
The role of scavenger receptor BI in hepatitis - eTheses Repository ...
The role of scavenger receptor BI in hepatitis - eTheses Repository ...
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108<br />
It would be more appropriate to measure mutant SR-<strong>BI</strong> <strong>receptor</strong> activity us<strong>in</strong>g<br />
an <strong>in</strong> vitro model <strong>of</strong> viral entry such as the HCVpp system. We therefore<br />
attempted to render CHO-SR-<strong>BI</strong> cells permissive to HCVpp <strong>in</strong>fection by<br />
exogenous expression <strong>of</strong> CD81 and CLDN1. <strong>The</strong>se cells were readily <strong>in</strong>fected<br />
by control pseudo-particles express<strong>in</strong>g VSV glycoprote<strong>in</strong>s, <strong>in</strong>dicat<strong>in</strong>g that<br />
CHO cells support the expression <strong>of</strong> the GFP reporter gene, however HCVpp<br />
failed to <strong>in</strong>fect the cells (data not shown). This suggests that either the HCV<br />
<strong>receptor</strong>s are <strong>in</strong>appropriately expressed <strong>in</strong> a CHO cell background or further<br />
co-<strong>receptor</strong>(s) await identification.<br />
In the time s<strong>in</strong>ce this work was completed reports have <strong>in</strong>dicated that residues<br />
119, 153, 163 and 168 <strong>of</strong> the SR-<strong>BI</strong> extracellular loop may be important for E2<br />
<strong>in</strong>teraction (J.Bwanali et. al. 14th International Symposium on HCV and<br />
personal communication); the mutants used <strong>in</strong> this study do not cover these<br />
sites. <strong>The</strong>se putative E2 b<strong>in</strong>d<strong>in</strong>g residues are not currently believed to be<br />
<strong>in</strong>volved <strong>in</strong> the <strong>in</strong>teraction <strong>of</strong> SR-<strong>BI</strong> with any <strong>of</strong> its natural ligands, however it<br />
would be <strong>in</strong>terest<strong>in</strong>g to study whether SR-<strong>BI</strong> rema<strong>in</strong>s biologically functional<br />
when engaged by HCV.<br />
A recent publication on Plasmodium <strong>in</strong>fection <strong>of</strong> hepatocytes suggests that<br />
SR-<strong>BI</strong> mediated delivery <strong>of</strong> cholesterol directly to the plasma membrane alters<br />
CD81 localisation, result<strong>in</strong>g <strong>in</strong> <strong>in</strong>creased Sporozoite <strong>in</strong>vasion (339). <strong>The</strong> two<br />
SR-<strong>BI</strong> mutants unable to mediate selective cholesterol transfer (Table 3-1),