Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.
PLoS Comput Biol. 2011 Oct;7(10):e1002185. doi: 10.1371/journal.pcbi.1002185. Epub 2011 Oct 13.
Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100-150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence.
最近的数据表明，HIV-1 的特征是病毒毒力因素在感染之间具有遗传性的变化，这表明病毒毒力可以在人群水平上自然选择。传染性和感染持续时间之间的权衡似乎有利于中等毒力的病毒。我们开发了一个数学模型来模拟毒力不同的假定病毒基因型的动态。我们使用病毒载量（SPVL）作为毒力的替代指标，这是无症状感染期间血液中病毒颗粒的稳定密度。突变、生存和传染性对 SPVL 的依赖性以及宿主效应被纳入模型。该模型被拟合到数据中以估计未知参数，并发现它很好地拟合了现有数据。参数的最大似然估计产生了一个模型，其中 SPVL 从任何初始条件收敛到 HIV-1 首次出现后 100-150 年内的观察值。我们估计了 1）宿主效应和 2）病毒毒力基因型在下一次感染中突变的程度，并发现这两个参数在解释 SPVL 的变化方面存在权衡。该模型证实，向中等水平的毒力进化速度足够快，足以在 HIV 流行的早期阶段发生，并且证实了给定对进化的假设限制，现有的病毒载量几乎是最优的。该模型为检查 HIV-1 毒力的未来进化提供了一个有用的框架。
