The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection
The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection
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DOI：
10.1371/journal.ppat.1004112
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发表时间：
2014-05-01
期刊：
影响因子：
6.7
通讯作者：
Brown, Andrew J. Leigh
中科院分区：
文献类型：
--
作者：
Hodcroft, Emma;Hadfield, Jarrod D.;Brown, Andrew J. Leigh
艾滋病毒感染者的疾病进展差异很大，虽然影响这种变异的环境和宿主因素已被广泛研究，但病毒对疾病进展预测指标--设定点病毒载量变异的影响尚不清楚。以前的研究使用传递对和对少量个体的系统发育信号进行分析，已经产生了广泛的病毒遗传效应估计。在这里，我们提出了一种基于数量遗传学的种群规模方法的新应用，以非常大的数据集为基础，估计英国B亚型HIV-1疫情中病毒遗传对设定点病毒载量的影响。分析8,483名患者在抗逆转录病毒治疗前的初始病毒载量和相关的Poll序列，我们估计由病毒遗传效应解释的病毒载量变异比例为5.7%(可信区间为2.8-8.6%)。我们还估计，由于对病毒的选择和环境影响，随着时间的推移，病毒载量的变化将下降0.05log(10)拷贝/毫升/年，而最近的研究表明，过去20年报告的病毒载量小幅增加可能是由于病毒的进化变化。我们的结果表明，在英国疫情中，B亚型对病毒载量有轻微但显著的病毒遗传影响。通过允许分析大样本大小，我们预计我们的方法将适用于估计许多生物体中对性状的遗传贡献。
Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log(10) copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.