CD4 and infection: Infection of RMs with pathogenic SIVs and SHIVs of different coreceptor usage, therefore, recapitulates key features of HIV infection and pathogenesis in humans: R5 SIV/SHIV infection induces a disease course that is more similar to that which occurs during most human infections with HIV-1, while X4 SIV/SHIV infection reproduces the precipitous peripheral CD4+ T cell decline observed in patients infected with X4 HIV-1 isolates or in late stage disease concomitant with the emergence of X4 virus.