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

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16<br />

HCV targets and enters hepatocytes via at least 3 <strong>receptor</strong>s; CD81,<br />

<strong>scavenger</strong> <strong>receptor</strong> B-I (SR-<strong>BI</strong>) and claud<strong>in</strong>-1 (CLDN1) (91, 120, 179), this<br />

process will be covered <strong>in</strong> section 1.4. After entry to the cytoplasm the HCV<br />

genome acts as an mRNA for the production <strong>of</strong> a s<strong>in</strong>gle 3000 am<strong>in</strong>o acid<br />

polyprote<strong>in</strong>. Unlike some Flaviviruses such as dengue, HCV lacks a 5’ cap<br />

and as such <strong>in</strong>itiates translation via an <strong>in</strong>ternal ribosomal entry site (IRES).<br />

<strong>The</strong> IRES is found <strong>in</strong> the 5’ UTR and conta<strong>in</strong>s a series <strong>of</strong> RNA stem loop<br />

structures which <strong>in</strong>itiate translation by br<strong>in</strong>g<strong>in</strong>g the 40s ribosomal subunit <strong>in</strong>to<br />

contact with the viral start codon (18, 251, 318)<br />

<strong>The</strong> polyprote<strong>in</strong> comprises 10 prote<strong>in</strong>s, the structural prote<strong>in</strong>s, Core, E1 and<br />

E2 are found at the am<strong>in</strong>o term<strong>in</strong>us and the non-structural prote<strong>in</strong>s p7-NS5B<br />

comprise the rema<strong>in</strong>der. Upon its translation a series <strong>of</strong> trans-membrane<br />

doma<strong>in</strong>s anchor the polyprote<strong>in</strong> to the endoplasmic reticulum (Figure 1-2)<br />

(181, 241). <strong>The</strong>re is an alternate read<strong>in</strong>g frame with<strong>in</strong> the HCV genome<br />

whereby a ribosomal frameshift with<strong>in</strong> the core region yields a series <strong>of</strong><br />

prote<strong>in</strong> products <strong>of</strong> unknown function (46, 255).

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