Session 60Poster Presentations Primary HIV/SIV Infection Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall A
511 The Role of Target Cells and Specific Immunity in Primary SIV Infection R. R. Regoes*1, R. Antia1, D. Garber2, G. Silvestri2, M. B. Feinberg1,2, S. I. Staprans1,2 1Emory Univ, Atlanta GA and 2Emory Vaccine Res Ctr, Atlanta GA
Background: The virus load shortly after the primary infection is one of the best correlates of disease progression. Therefore, an understanding of the factors governing primary HIV infection is crucial for the design of rational treatment and vaccination strategies. Two main hypotheses of the driving force of primary HIV infection have been proposed. According to one hypothesis, early viral replication is controlled by specific cellular immune responses to the virus. The alternative hypothesis proposes that a lack of target cells is responsible for controlling viral replication during primary infection.
Methods: We used a novel mathematical modeling scheme to investigate the factors governing early viral replication in eight SIV-infected rhesus macaques. The experiment we analyzed involved frequent measurements of the virus load, of various CD4+ T-cell subpopulations, and of SIV-specific CD8+ T-cells in 4 normal animals and 4 animals treated with a co-stimulatory inhibitor which abrogated SIV-specific cellular and humoral immune responses. We developed 2 simple mathematical models, one that describes the interaction between the virus and its target cells only and an extended model which additionally takes into account the inhibitory effect of specific CD8+ T-cells on viral replication. Comparing the goodness of fit of the two models with an F-test enabled us to determine whether specific CD8+ T-cells play a significant role in primary SIV infection.
Results: Fitting the 2 models to the treated animals showed that in 3 out of 4 animals, the specific CD8+ T-cell responses do not significantly inhibit viral replication. The animal for which the CD8+ T-cell responses were found to contribute to viral control showed levels of specific CD8+ T-cells comparable to the untreated animals. Applying our modeling scheme to the untreated animals showed that CD8+ T-cell responses significantly inhibit viral replication in all 4 animals. Furthermore, our analysis suggests that during primary infection virus-infected cells are killed mainly by CD8+ T-cell responses and not directly by the virus.
Conclusions: Our results show that the peak and the subsequent decline in the virus load, in the untreated animals, is not due to target cell limitation, but is driven to a large extent by specific CD8+ T-cells. We conclude that the level of SIV-specific CD8+ T-cells is an important determinant of early viral replication.
