(A) Pearson’s correlation of CD8⁺Ki-67⁺ fraction with MKI67 gene expression in SIVmac239-infected RMs. Peripheral blood Ki-67⁺CD8⁺% was assessed using the gating strategy outlined in B and was correlated with MKI67 mRNA log₁₀ intensity in peripheral blood using Pearson’s correlation (false discovery rate corrected; P < 0.00106). (B) Representative density plot of flow cytometry analysis for expression of Ki-67⁺ on gated CD3⁺CD8⁺ T cells in PBMCs of SIVmac239-infected RMs. The numbers denote the percentage of gated cells, indicating the fraction of CD3⁺ T cells expressing CD4 or CD8 (left panels) or the fraction of CD3⁺CD8⁺ T cells expressing Ki-67 (right panels) from a time point prior to SIV infection and from day 31 after infection in the same animal. (C) Longitudinal expression profile of Ki-67 protein on CD3⁺CD8⁺ T cells as measured by flow cytometry; error bars indicate SEM. (D) MIK67 mRNA as measured by microarray. MKI67 gene expression is the average ratio of gene expression relative to preinfected samples. (E) Longitudinal profiles of 4 genes whose expression significantly correlated with CD8⁺Ki-67⁺ percentage in peripheral blood and identified in the literature as related to immune activation, CD8⁺ T cell exhaustion, or HIV pathogenesis. (F) Model of immunomodulation during SIV infection of natural hosts and during pathogenic infection, demonstrating differences in ISG induction and immunoregulatory gene expression; details in text.