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reduction in the rate of adaptation, mainly by slowing the second phase (Fig. 2.13).
Therefore, under the simulation conditions described here, cell superinfection had a
minor effect on the rate of adaptation, but recombination appears to hasten adaptation
substantially.
2.6.5 Adaptation to Antibody Surveillance
2.6.5.1 Functional and Neutralization Components of Fitness
To inves-
tigate the relationship between the functional and neutralization components of fitness,
selection by antibodies was added to the simulation. In this simulation, the production
of antibodies with increased affinity for their epitope is stimulated when the epitopes
are detected in the viral population.
As in the previous simulations, adaptation to CCR5 is observed as an increase
in the functional component of fitness, but in this case, this component does not
remain near one indefinitely (Fig. 2.14). Rather, the functional component begins to
decline after 75 generations. This is due to the emergence of a neutralization escape
mutant as seen in the increase in the neutralization component after an initial decrease.
The neutralization component begins at 1, because antibody production has not been
stimulated at generation 0, and decreases as the potency of antibodies increases. The
increase in the neutralization component at generation 75 indicates that a viral variant
with a previously unrecognized epitope is spreading in the population. However, this
variant is suboptimal in its interaction with CCR5, resulting in a concomitant decline
in the functional component of fitness.
Then, the neutralization component decreases shortly after it began to increase
due to a new antibody response, and this coincides with stabilization of the functional
Figure 2.14
The changes in total fitness, and the functional and neutralization components of
fitness over time. Curves are based on means of 20 replicate simulations and bars are standard
deviations across replicates.
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