A predictive fitness model for influenza
A predictive fitness model for influenza
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DOI：
10.1038/nature13087
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发表时间：
2014-03-06
期刊：
影响因子：
64.8
通讯作者：
Laessig, Michael
中科院分区：
文献类型：
--
作者：
Luksza, Marta;Laessig, Michael
季节性人类流感A/H3N2型病毒经历了快速进化，这在流行毒株种群中产生了每年显著的序列更替。适应性突变响应人类免疫挑战，主要发生在抗原表位，即病毒表面蛋白血凝素的抗体结合域。在这里，我们开发了一个血凝素的适应度模型，该模型预测了病毒种群从一年到明年的演变。有两个因素决定了菌株的适合性：适应性表位变化和表位外的有害突变。我们使用以前所有菌株的群体遗传数据，推断出在给定年份中流通的菌株的两个适应度成分。根据每个菌株的适合度和频率，我们预测了下一年其后代菌株的频率。这种适应性模型描绘了甲型流感的适应历史，并为疫苗选择提出了一种原则性方法。我们的结果呼吁对流感和其他快速进化的病原体进行更全面的流行病学研究，通过基因连锁将抗原表型与其他病毒功能结合起来。
The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. Here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a strain: adaptive epitope changes and deleterious mutations outside the epitopes. We infer both fitness components for the strains circulating in a given year, using population-genetic data of all previous strains. From fitness and frequency of each strain, we predict the frequency of its descendent strains in the following year. This fitness model maps the adaptive history of influenza A and suggests a principled method for vaccine selection. Our results call for a more comprehensive epidemiology of influenza and other fast-evolving pathogens that integrates antigenic phenotypes with other viral functions coupled by genetic linkage.