Immunovirological Analyses of Chronically Simian Immunodeficiency Virus SIVmnd-1- and SIVmnd-2-Infected Mandrills (Mandrillus sphinx)^▿

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   Fig. 1.

   Plasma viral loads in SIVmnd-1-infected, SIVmnd-2-infected, and SIVmnd-1 and SIVmnd-2-coinfected mandrills. No significant difference was observed between the three groups. In coinfected mandrills, SIVmnd-2, the major replicative form, is responsible for the bulk of viral replication. Horizontal lines represent geometric means.
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   Fig. 2.

   CD4⁺ T cell counts in SIVmnd-infected mandrills. (a) Comparison of CD4⁺ T cell and CD8⁺ T cell counts (cells/μl) in SIVmnd-1-infected, SIVmnd-2-infected, SIVmnd-1 and SIVmnd-2-coinfected, and uninfected mandrills (P values were determined by the Mann-Whitney U test). Boxes, mean CD4⁺ T cell counts; bars, standard deviation; p = NS, the P value of the correlation coefficient was >0.05 (Spearman rank correlation test), i.e., not significant (NS). (b) Lack of correlation between CD4⁺ T cell counts (cells/μl) and ages of the animals (years) in the same cohort of mandrills. (c) Detailed analysis of CD4⁺ T cells counts in relation to the animal ages and genders for SIVmnd-1-infected, SIVmnd-2-infected, and SIVmnd-1 and SIVmnd-2-coinfected mandrills. (d) Lack of correlation between CD4⁺ T cell counts (cells/μl) and viral loads in the SIVmnd-infected animals.
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   Fig. 3.

   Assessment of CD4⁺ and CD8⁺ T cell subsets in SIV-infected and uninfected mandrills in peripheral blood. Summary of the relative proportion of CD3⁺ CD4⁺ (a) and CD3⁺ CD8⁺ (b) naive, memory (T_M), and effector (T_E) cells in lymphocytes isolated from peripheral blood. The correlation between the absolute number (cells/μl) of CD3⁺ CD4⁺ (c) and CD3⁺ CD8⁺ (d) naive, memory, and effector cells in SIVmnd-infected and uninfected mandrills demonstrates that in mandrills infected with SIVmnd-2 and coinfected with SIVmnd types 1 and 2 there is an expansion of effector cells. Lines in panels a and b represent average values.
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   Fig. 4.

   Cytokine production by CD4⁺ (left) and CD8⁺ (right) T cells. (a) No significant difference in IFN-γ production was observed between SIVmnd-1-infected, SIVmnd-2-infected, or SIVmnd-1 and SIVmnd-2-coinfected mandrills compared to SIV-uninfected mandrills. (b) Production of TNF-α by CD4⁺ T cells was not significantly different between the different groups; however, significantly higher levels of TNF-α were produced by CD8⁺ T cells from infected mandrills than uninfected mandrills, with the highest levels being observed in SIVmnd-2-infected mandrills. Lines represent average values.
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   Fig. 5.

   Assessment of T cell proliferation (Ki-67) in SIVmnd-infected mandrills. No significant increase of proliferating CD4⁺ (left) and CD8⁺ (right) T cells was observed in SIVmnd-1-infected, SIVmnd-2-infected, or SIVmnd-1 and SIVmnd-2-coinfected mandrills compared to SIV-uninfected mandrills (a). Levels of T cell proliferation did not correlate with either viral loads (b) or CD4⁺ (left) or CD8⁺ (right) T cell counts (c). Lines in panel a represent average values.
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   Fig. 6.

   Assessment of spontaneous and activation-induced in vitro T cell apoptosis in SIV-infected and uninfected mandrills using the staining assay for 7-AAD and annexin V (AnnV). Apoptosis was measured at baseline and after 24 and 48 h in the presence or absence of ConA. Similarly to what was observed in SMs and AGMs, SIV-infected MNDs reveal levels of T cell apoptosis comparable to those of uninfected animals. Low levels of baseline and spontaneous (after 48 h without any stimulus) T cell apoptosis were observed in both SIV-infected and uninfected mandrills. No statistically significant differences in the rates of baseline, spontaneous, and activation-induced (following 48 h of ConA stimulation) apoptosis, measured as rates of annexin V-positive cells, in either CD4⁺ or CD8⁺ T cells were observed between SIV-infected and uninfected MNDs. Boxes, mean for annexin V-positive cells; bars, standard deviation; 1, SIVmnd-1; 2, SIVmnd-2; 1 + 2, coinfection; Neg, SIVmnd negative.

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