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Comparative Study
. 2010 Aug 26;6(8):e1000901.
doi: 10.1371/journal.pcbi.1000901.

Similar impact of CD8+ T cell responses on early virus dynamics during SIV infections of rhesus macaques and sooty mangabeys

Roger D Kouyos  1 , Shari N Gordon, Silvija I Staprans, Guido Silvestri, Roland R Regoes
Affiliations
Comparative Study

Similar impact of CD8+ T cell responses on early virus dynamics during SIV infections of rhesus macaques and sooty mangabeys

Roger D Kouyos et al. PLoS Comput Biol. .

Abstract

Despite comparable levels of virus replication, simian immunodeficiency viruses (SIV) infection is non-pathogenic in natural hosts, such as sooty mangabeys (SM), whereas it is pathogenic in non-natural hosts, such as rhesus macaques (RM). Comparative studies of pathogenic and non-pathogenic SIV infection can thus shed light on the role of specific factors in SIV pathogenesis. Here, we determine the impact of target-cell limitation, CD8+ T cells, and Natural Killer (NK) cells on virus replication in the early SIV infection. To this end, we fit previously published data of experimental SIV infections in SMs and RMs with mathematical models incorporating these factors and assess to what extent the inclusion of individual factors determines the quality of the fits. We find that for both rhesus macaques and sooty mangabeys, target-cell limitation alone cannot explain the control of early virus replication, whereas including CD8+ T cells into the models significantly improves the fits. By contrast, including NK cells does only significantly improve the fits in SMs. These findings have important implications for our understanding of SIV pathogenesis as they suggest that the level of early CD8+ T cell responses is not the key difference between pathogenic and non-pathogenic SIV infection.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Measurements of virus loads and cell counts.
Measurements of virus load (first row), proliferating CD4+ T-cells (second row), proliferating CD8+ T-cells (third row), and NK cells (fourth row) in sooty mangabeys and rhesus macaques.
Figure 2
Figure 2. Illustration of the model comparisons.
Comparisons i) and iii) test whether taking CD8+ T cells into account improves the fits of the target-cell model and the NK model, respectively. Comparisons ii) and iv) test whether taking NK cells into account improves the fits of the target-cell model and the CD8+ T cell model respectively.
Figure 3
Figure 3. Best fits of virus load data.
Best fits by the target-cell model (black lines) and the CD8+ T cell model (green lines) of the virus load measurements (red dots) of sooty mangabeys and rhesus macaques.
See this image and copyright information in PMC

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