Immuno-epidemiological Modeling of HIV-1 Predicts High Heritability of the Set-Point Virus Load, while Selection for CTL Escape Dominates Virulence Evolution

In the absence of treatment, HIV-1 leads to AIDS, but this can take several years. The rate of disease progression is correlated to the set-point viral load (SPVL): a relatively constant number of virions per mL of blood that is established after the acute infection. The SPVL also has an influence on the transmission rate: individuals with higher SPVL tend to be more infectious. These two factors result in a trade-off where over the course of an infection, intermediate SPVLs lead to the most secondary infections. The SPVL in the population varies orders of magnitude, and has been shown to be heritable from transmitter to recipient. This means that SPVL is subject to Darwinian selection, and it has been shown that in populations the SPVL distribution and the transmission trade-off curve overlap: the most common SPVL values in the population are associated with the most secondary infections. This observation makes a lot of sense at first glance, but ignores two important aspects: within-host selection for immune escape and host-heterogeneity of the immune system. In this paper, we investigate if we can also make sense of these SPVL-related observations if we take the immune system into account. The answer is: “no”.

Recommended citation: van Dorp, CH. et al (2014). "Immuno-epidemiological Modeling of HIV-1 Predicts High Heritability of the Set-Point Virus Load, while Selection for CTL Escape Dominates Virulence Evolution." PLOS Computational Biology. 10(12): e1003899.
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