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

28
in HepG2 cells (101). These data indicate that using recombinant soluble
proteins to measure E2-receptor interactions can be a poor model of infection.
They also established that soluble CD81 LEL neutralisation of HCVpp occurs
after virion binding to target cells (101), suggesting that CD81 is not the
primary HCV attachment receptor, a view supported by other findings (31, 91,
346).
The use of anti-E2 mAbs and comparison of diverse envelope proteins
allowed the identification of putative CD81 recognition domains within the
major HCV glycoprotein. Mutagenic studies within these regions has both
confirmed and eliminated candidate residues. The currently accepted CD81
binding regions are 436-443, 527-535 and 612-619, residue 420 is also
involved (81, 99, 237, 265). However, without a crystal structure of HCV E2 it
remains unclear how these distant regions engage CD81 and whether other
receptors are required to promote CD81 interaction. Antibodies that recognise
sites within CD81 binding regions are neutralising and work to develop a
vaccine that targets these epitopes is ongoing (145, 147, 236, 237, 307).
Scavenger receptor B-I (SR-BI)
SR-BI is a multi-ligand lipoprotein receptor, it is expressed throughout the
body but is predominantly found in the liver and steroidogenic tissue (161). It
resides at the plasma membrane, with two transmembrane domains
separated by a large extracellular region responsible for ligand binding (161).
Its functions are varied and will be covered in more detail in a later section.
However its major role within the liver is the uptake of cholesterol from high