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

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There are various models of how antibody binding prevents virus attachment,
entry and penetration, the most simplistic view is of a particle coated with
antibodies unable to function due to stearic hindrance exerted by the antibody
shell (54). However, neutralisation efficiency does not necessarily directly
correlate with the degree of antibody coating, indeed in some cases particles
saturated with mAb remain infectious (97). Therefore more sophisticated
models have been developed to accommodate such experimental data.
Multiple hit and occupancy models of neutralisation draw upon the concept
that virions carry numerous copies of glycoprotein(s) required for virus entry,
however particle entry may only require a fraction of the total number to be
functional (151). Therefore, a particle can tolerate antibody mediated
inactivation of multiple envelope proteins without any appreciable reduction in
infectious potential. Experimentally, this phenomena manifests itself as a lag
in neutralisation, whereby at lower antibody concentrations there is no
detectable inhibition (105, 152).
The importance of epitopes targeted by humoral responses cannot be
overlooked. Ligation of some epitopes may exert moderate to weak
neutralisation by partial inhibition of envelope protein function. Other, so called
critical epitopes, contribute directly to events such as receptor engagement;
blocking of these will render an envelope protein completely inactive (152).
Consequently, antibodies that target critical epitopes can exhibit strong
neutralisation at low occupancy; that is to say relatively few epitopes are
‘occupied’ per particle (228). It has been reported that for some viruses the
binding of a single antibody is sufficient to inactivate a particle, in these cases