Thus, while we cannot completely exclude the possibility that less efficient GPR15 and CXCR6 use by CD4-independent variants may limit infection of GPR15+ or CXCR6+ cells in vivo, we think it is more likely that this feature reflects simply another aspect of the overall more coreceptor-constrained, less plastic function of the CD4-independent Envs. Here, GPR15 is linked to infection.