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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Particle density is believed to be determ<strong>in</strong>ed by lipid composition; lower<br />
density HCV virions have a higher lipid content and therefore may be<br />
regarded as the ‘most lipoprote<strong>in</strong> like’ form. Low density HCV have the<br />
highest specific <strong>in</strong>fectivity (45, 179, 180) and we have shown that particle<br />
density correlates with sensitivity to neutralis<strong>in</strong>g antibodies (Figure 5-8).<br />
Taken together these observations suggest that adopt<strong>in</strong>g a lipoprote<strong>in</strong> like<br />
formation promotes HCV <strong>in</strong>fection, and possibly stabilises the virion<br />
glycoprote<strong>in</strong>s <strong>in</strong> a manner that reduces epitope availability. A number <strong>of</strong><br />
apoprote<strong>in</strong> species can be found <strong>in</strong> HCV LVPs, <strong>in</strong>deed apoC-I is thought to<br />
enhance <strong>in</strong>fection (79, 210, 211), however it is not known how apoprote<strong>in</strong>s<br />
function with<strong>in</strong> an <strong>in</strong>fectious particle. Understand<strong>in</strong>g the <strong>role</strong> <strong>of</strong> apoprote<strong>in</strong>s<br />
with<strong>in</strong> circulat<strong>in</strong>g HCV particles will be key to determ<strong>in</strong><strong>in</strong>g the relationship<br />
between particle density and <strong>in</strong>fectivity.<br />
Figure 6-2 displays a model structure <strong>of</strong> a HCV LVP; this particle has both<br />
virion and lipoprote<strong>in</strong> like characteristics. <strong>The</strong> envelope prote<strong>in</strong>s lie flat with<strong>in</strong><br />
the membrane surround<strong>in</strong>g the capsid, however the outer leaflet <strong>of</strong> the virion<br />
envelope is fused with the lipoprote<strong>in</strong> lipid monolayer. This proposed structure<br />
would conf<strong>in</strong>e the viral glycoprote<strong>in</strong>s to the virion envelope bilayer, whereas<br />
the very large structural apoprote<strong>in</strong>, apo-B100, resides with<strong>in</strong> the triglyceride<br />
core <strong>of</strong> lipoprote<strong>in</strong> (321) and should not diffuse <strong>in</strong>to the virion. However, the<br />
smaller exchangeable apoprote<strong>in</strong>s reside with<strong>in</strong> the lipoprote<strong>in</strong> lipid monolayer<br />
(321), allow<strong>in</strong>g their diffusion throughout the particle and <strong>in</strong>teraction with viral<br />
glycoprote<strong>in</strong>s. <strong>The</strong> areas <strong>of</strong> the viral envelope prote<strong>in</strong>s shaded <strong>in</strong> green