Bonhoeffer Sebastian, Fraser Christophe, Leventhal Gabriel E
Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
PLoS Pathog. 2015 Feb 6;11(2):e1004634. doi: 10.1371/journal.ppat.1004634. eCollection 2015 Feb.
Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis.
HIV患者的设定点病毒载量范围跨越几个数量级,是HIV疾病进展的关键决定因素。最近的一些研究报告了设定点病毒载量的高遗传性,这意味着病毒遗传因素在很大程度上导致了病毒载量的总体差异。考虑到与控制病毒感染相关的宿主因素的多样性,这种高遗传性令人惊讶。在这里,我们开发了一个分析模型,该模型将设定点病毒载量分布的时间变化描述为遗传性的函数。该模型表明,高遗传性是对观察到的设定点病毒载量方差的最简约解释。因此,我们的结果不仅加强了先前遗传性估计的可信度,还为病毒发病机制提供了新的见解。