Thus, we conclude that while the selective pressure for infection of alternative target cells with lower receptor expression levels is present in RPs with and without coreceptor switch, R5 viruses in macaques that did not switch evolved to be more sCD4 sensitive and infected CD4low cells more efficiently via a mechanism other than adoption of an “open” Env conformation to expose their CD4BS for better receptor binding. Here, ERVW-1 is linked to infection.