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In vivo evolutionary dynamics of HIV-1 in the follicular and extra-follicular compartments of the lymphoid tissues
In the secondary lymphoid tissues, human immunodeficiency virus (HIV) can replicate both in the follicular and the extrafollicular compartments. Yet, virus is concentrated in the follicular compartment in the absence of antiretroviral therapy, in part due to the lack of cytotoxic T lymphocyte (CTL)-mediated activity there. CTL home to the extrafollicular compartment, where they can suppress virus load to relatively low levels. We use mathematical models to show that this compartmentalization can explain seemingly counterintuitive observations. First, it can explain the observed constancy of the viral decline slope during antiviral therapy irrespective of the presence of CTL in SIV-infected macaques, under the assumption that CTL-mediated lysis significantly contributes to virus suppression. Second, it can account for the relatively long times it takes for CTL escape mutants to emerge during chronic infection even if CTL-mediated lysis is responsible for virus suppression. Third, the compartmental structure has important implications for the evolution of viral mutants in general, influencing mutant fixation probabilities and fixation times. The talk will discuss these results.