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. 2006 Apr 3:3:22.
doi: 10.1186/1743-422X-3-22.

Role of CD8+ cells in controlling replication of nonpathogenic Simian Immunodeficiency Virus SIVmac1A11

Koen K A Van Rompay  1 , Emily J Blackwood, Gary Landucci, Don Forthal, Marta L Marthas
Affiliations

Role of CD8+ cells in controlling replication of nonpathogenic Simian Immunodeficiency Virus SIVmac1A11

Koen K A Van Rompay et al. Virol J. .

Abstract

Infection of macaques with the avirulent molecular clone SIVmac1A11 results in transient low viremia and no disease. To investigate if this low viremia is solely due to intrinsic poor replication fitness or is mediated by efficient immune-mediated control, 5 macaques were inoculated intravenously with SIVmac1A11. Three animals that were depleted of CD8+ cells at the start of infection had more prolonged viremia with peak virus levels 1 to 2 logs higher than those of 2 animals that received a non-depleting control antibody. Thus, CD8+ cell-mediated immune responses play an important role in controlling SIVmac1A11 replication during acute viremia.

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Figures

Figure 1
Figure 1
Effect of CD8+ cell depletion on SIVmac1A11 infection: viral and immunologic parameters. Five animals were inoculated with SIVmac1A11 at time zero. Three animals were CD8+ cell depleted via administration of cM-T807 while the other 2 animals received control antibody. (A) Viral RNA levels in plasma (measured by bDNA assay, with a limit of detection of 125 copies/ml; [18]). Results from virus isolation from 1 million PBMC, using CEMx174 cells and p27 measurement [34] are given as positive (+) or negative (-). The absolute counts of CD8+CD3+ T lymphocytes, CD8+CD3- NK cells and CD4+CD3+ T lymphocytes were measured according to flow cytometry techniques described previously [18], and are presented in graphs B through D, respectively. (E) SIV-specific IgG titers measured by a whole SIV ELISA [29]; although the CD8+ cell depleted animals made a faster response than the undepleted animals, from week 6 onwards, both animal groups had similar antiviral IgG titers (1: 6,400 to 1: 25,600). (F) Antiviral activity of plasma collected at 17 days after SIVmac1A11 inoculation as measured in a ADCVI assay, described in detail elsewhere (Forthal et al., submitted for publication). Briefly, CEMx174 cells were infected with SIVmac1A11 at a MOI of 0.01; 48 hours later, cells were plated in 96-well plates at 50,000 cells per well. Plasma samples (including negative and positive control samples) were added at a 1:100 dilution and human PBMC effector cells were added to obtain an effector:target cell ratio of 10:1. Five days later, SIV p27 was measured in supernatant fluid using a commercially available ELISA (Zeptometrix Corporation, Buffalo, NY). Percent inhibition by the plasma samples collected on day 17 was calculated relative to the level of virus replication in the presence of plasma collected on day zero (before SIVmac1A11 inoculation); the presented values represent mean +/- SEM of 4 separate assays (with effector PBMC of 4 different donors). In the absence of effector cells, no significant inhibition (≤ 11%) was observed (data not shown).
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