This figure shows how, in SIV-infected SMs (natural hosts), low immune activation, expressed as the fraction of CD4⁺ T cell clones that undergo activation at any given time, may act in concert with reduced and/or delayed expression of CCR5 in promoting a steady state where immune system homeostasis is preserved despite high virus replication. The top row shows how in HIV-infected humans and SIV-infected RMs, presence of a high fraction of activated CD4⁺ T cell clones results in the rapid accumulation of CD4⁺ T cells expressing CCR5 that are infected and killed by the virus, resulting in the disruption of the homeostasis of these activated clones. In SIV-infected SMs (bottom row), a smaller fraction of CD4⁺ T cells clones are activated, but a delayed and reduced expression of CCR5 on these cells may allow for their accumulation, resulting in an equally high level of virus replication when CCR5 is finally expressed. In this case, however, the homeostasis of fewer CD4⁺ T cells clones is disrupted at any given time.