FIG. 6.

Model for evolution of coreceptor tropism. R5-tropic viruses are represented in white, dual-R viruses in light gray, and dual-X/X4 viruses in dark gray. The top panel shows the introduction of mutations associated with CXCR4 tropism in the V3 loop of an R5 virus results in X4-tropic or dual-X progeny that have a large fitness disadvantage relative to the parental strain (indicated by an X). The bottom panel shows how the acquisition of non-V3 env mutations which confer low-level CXCR4 use, while maintaining efficient CCR5 use (dual-R viruses), leads to strains that may have a fitness advantage and correspond to precursors of dual-X or X4 viruses. See the Discussion for details.