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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42<br />
(204). Other <strong>in</strong>vestigations have correlated CLDN1 junctional localisation to<br />
HCV permissivity, however these studies were carried us<strong>in</strong>g m<strong>in</strong>imally or non-<br />
polarised cell types (342). <strong>The</strong> search for an appropriate polarised hepatic cell<br />
l<strong>in</strong>e is ongo<strong>in</strong>g.<br />
A recent report has raised the prospect <strong>of</strong> tissue specific factors that may<br />
<strong>in</strong>terfere with the <strong>in</strong>teraction <strong>of</strong> HCV and its co-<strong>receptor</strong>s (261). <strong>The</strong><br />
tetraspan<strong>in</strong> web <strong>in</strong> which CD81 resides conta<strong>in</strong>s numerous partner molecules<br />
that contribute to the characteristics <strong>of</strong> the membrane doma<strong>in</strong>. EWI-2 is a<br />
member <strong>of</strong> the immunoglobul<strong>in</strong> super-family and conta<strong>in</strong>s a unique glutam<strong>in</strong>e-<br />
tryptophan-isoleuc<strong>in</strong>e (EWI) motif, it is a major partner <strong>of</strong> CD81 and is<br />
believed to mediate <strong>in</strong>teractions between the web and underly<strong>in</strong>g cytoskeleton<br />
(271). Interest<strong>in</strong>gly a tissue specific EWI-2 cleavage product, EWI-2w<strong>in</strong>t (EWI-<br />
2 without its N-term<strong>in</strong>us), is able to block HCV E2 <strong>in</strong>teraction with CD81 and<br />
<strong>in</strong>troduction <strong>of</strong> EWI-2w<strong>in</strong>t <strong>in</strong>to permissive hepatoma cells reduces HCVcc/pp<br />
<strong>in</strong>fection (261). <strong>The</strong> proteolytic cleavage necessary for EWI-2w<strong>in</strong>t expression<br />
does not occur <strong>in</strong> permissive cells, suggest<strong>in</strong>g that an <strong>in</strong>hibitory prote<strong>in</strong> may<br />
determ<strong>in</strong>e HCV liver tropism.<br />
<strong>The</strong> process <strong>of</strong> characteris<strong>in</strong>g the series <strong>of</strong> virus-<strong>receptor</strong> and <strong>receptor</strong>-<br />
<strong>receptor</strong> <strong>in</strong>teractions necessary for HCV <strong>in</strong>fection has only just begun; the<br />
rather disparate nature <strong>of</strong> our current knowledge reflects this. However, as the<br />
field develops we will be able to consolidate our understand<strong>in</strong>g <strong>of</strong> the complex<br />
relationships with<strong>in</strong> a permissive cell allow<strong>in</strong>g a global perspective on HCV<br />
attachment and entry.