Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives
Figure 2
Neutralizing occupancies over heterogeneous populations of enveloped viruses. Two enveloped virions are pictured. Each has twelve glycoprotein spikes schematically displayed, for clarity only at the circumference. Functional spikes are shown in blue, decayed or otherwise nonfunctional ones in grey. Both virions have seven functional and five nonfunctional spikes but with different distributions over the two virion surfaces. If a virion requires a certain number of spikes in contiguity to form an entry complex and the spikes cannot move freely over the virion surface, the two different distributions will confer different neutralization sensitivities. The virion to the left is neutralized: three NAb molecules inactivate the constellation of active spikes and one binds redundantly to an inactive spike. The virion to the right is also neutralized but by only two NAb molecules, one inactivating a group of three spikes (three adjacent ones being postulated here to be the bare minimum for entry) and one binding redundantly to a spike that is functional but inert through lack of active neighbors. Effects of this sort could blur critical occupancy thresholds and reduce the steepness of neutralization curves in experiments with phenotypically mixed virus, of which the virions carry random assortments of antigenic and nonantigenic subunits of the envelope glycoprotein oligomers. Heterogeneity of the number (not shown) and distribution (shown) of functional entry-mediating viral proteins may explain how different occupancies are required for blocking viral entry. Some of these considerations apply also to naked viruses.
