Compartmental structure in the secondary lymphoid tissue can slow down

Human immunodeficiency virus (HIV-1) replicates in the secondary lymphoid tissues, which are characterized by complex compartmental structures. While cytotoxic T lymphocytes (CTL) readily access infected cells in the extrafollicular compartments, they do not home to follicular compartments, which thus represent an immune-privileged site. Using mathematical models, previous work has shown that this compartmental tissue structure can delay the emergence of CTL escape mutants. Here, we show computationally that the compartmental structure can have an impact on the evolution of advantageous mutants that are not related to CTL recognition: (i) compartmental structure can influence the fixation probability of an advantageous mutant, with weakened selection occurring if CTL responses are of intermediate strength; (ii) compartmental structure is predicted to reduce the rate of mutant generation, which becomes more pronounced for stronger CTL responses; and (iii) compartmental structure is predicted to slow down the overall rate of mutant invasion, with the effect becoming more pronounced for stronger CTL responses. Altogether, this work shows that