  The twin processes of viral evolutionary escape and reversion in response to
host immune pressure, in particular the cytotoxic T-lymphocyte (CTL) response,
shape Human Immunodeficiency Virus-1 sequence evolution in infected host
populations. The tempo of CTL escape and reversion is known to differ between
CTL escape variants in a given host population. Here, we ask: are rates of
escape and reversion comparable across infected host populations? For three
cohorts taken from three continents, we estimate escape and reversion rates at
23 escape sites in optimally defined Gag epitopes. We find consistent escape
rate estimates across the examined cohorts. Reversion rates are also consistent
between a Canadian and South African infected host population. Certain Gag
escape variants that incur a large replicative fitness cost are known to revert
rapidly upon transmission. However, the relationship between escape/reversion
rates and viral replicative capacity across a large number of epitopes has not
been interrogated. We investigate this relationship by examining $in$ $vitro$
replicative capacities of viral sequences with minimal variation: point escape
mutants induced in a lab strain. Remarkably, despite the complexities of
epistatic effects exemplified by pathways to escape in famous epitopes, and the
diversity of both hosts and viruses, CTL escape mutants which escape rapidly
tend to be those with the highest replicative capacity when applied as a single
point mutation. Similarly, mutants inducing the greatest costs to viral
replicative capacity tend to revert more quickly. These data suggest that
escape rates in Gag are consistent across host populations, and that in general
these rates are dominated by site specific effects upon viral replicative
capacity.
