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 ...
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
58<br />
<strong>The</strong>se data po<strong>in</strong>t to a requirement for the VLDL assembly mach<strong>in</strong>ery for the<br />
packag<strong>in</strong>g <strong>of</strong> viral RNA and structural prote<strong>in</strong>s <strong>in</strong>to <strong>in</strong>fectious HCV LVP, which<br />
are trafficked via the secretory pathway to allow particle release. Intracellular<br />
particles are vulnerable to pre-secretory degradation (109), suggest<strong>in</strong>g that an<br />
<strong>in</strong>fected host cell treats HCV LVPs as VLDLs, target<strong>in</strong>g lipid poor forms for<br />
recycl<strong>in</strong>g <strong>in</strong> the absence <strong>of</strong> sufficient substrate(s).<br />
It is not yet clear how the virus structural prote<strong>in</strong>s and host apoprote<strong>in</strong>s<br />
associate dur<strong>in</strong>g particle assembly. However current data suggests that lipid<br />
droplets (LD), <strong>in</strong>tracellular organelles responsible for lipid storage, are central<br />
to this process. HCV genome replication is believed to occur on membranes<br />
<strong>in</strong> and around the endoplasmic reticulum, mature E1E2 heterodimers also<br />
reside there (181, 220). Core prote<strong>in</strong>, however, translocates to the LDs and is<br />
seen to coat their surface (41, 42, 215), NS5A also localises with the LDs<br />
(280), viral prote<strong>in</strong> association with LDs is essential for the production <strong>of</strong><br />
<strong>in</strong>fectious particles. Core directs the redistribution <strong>of</strong> LDs along the micro-<br />
tubule network br<strong>in</strong>g<strong>in</strong>g them <strong>in</strong>to the vic<strong>in</strong>ity <strong>of</strong> membranes bear<strong>in</strong>g genome<br />
replication complexes (41). It is currently believed that assembly occurs at<br />
these juxtapositions (41, 215), <strong>in</strong>deed numerous studies have demonstrated a<br />
accumulation <strong>of</strong> viral prote<strong>in</strong>s and RNA at these sites (131, 189, 215, 305).<br />
Furthermore, LDs provide a source <strong>of</strong> triglycerides for the load<strong>in</strong>g <strong>of</strong> lipids on<br />
to ApoB (321), suggest<strong>in</strong>g that the VLDL and HCV assembly pathways<br />
converge at this location. (Figure 1-5).