CD4 and infection: The conditions (e.g., extremely high levels of virus replication), genotypic requirements (i.e., V3 loop sequence changes) and pattern (e.g., emergence of neutralization sensitive X4 variants following the onset of CD4+ cell loss) for coreceptor switching in SHIVSF162P3N-infected macaques overlapped with those reported for HIV-1 infected humans [8], [9], [23], [24], [25], [26], [27], [28], supporting the use of this infection model to study the basis and underlying selection pressures for R5-to-X4 virus evolution in vivo.