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Canalization of the evolutionary trajectory of the human influenza virus

机译:人流感病毒进化轨迹的渠道化

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Background Since its emergence in 1968, influenza A (H3N2) has evolved extensively in genotype and antigenic phenotype. However, despite strong pressure to evolve away from human immunity and to diversify in antigenic phenotype, H3N2 influenza shows paradoxically limited genetic and antigenic diversity present at any one time. Here, we propose a simple model of antigenic evolution in the influenza virus that accounts for this apparent discrepancy. Results In this model, antigenic phenotype is represented by a N -dimensional vector, and virus mutations perturb phenotype within this continuous Euclidean space. We implement this model in a large-scale individual-based simulation, and in doing so, we find a remarkable correspondence between model behavior and observed influenza dynamics. This model displays rapid evolution but low standing diversity and simultaneously accounts for the epidemiological, genetic, antigenic, and geographical patterns displayed by the virus. We find that evolution away from existing human immunity results in rapid population turnover in the influenza virus and that this population turnover occurs primarily along a single antigenic axis. Conclusions Selective dynamics induce a canalized evolutionary trajectory, in which the evolutionary fate of the influenza population is surprisingly repeatable. In the model, the influenza population shows a 1- to 2-year timescale of repeatability, suggesting a window in which evolutionary dynamics could be, in theory, predictable.
机译:背景自从1968年出现以来,甲型流感(H3N2)在基因型和抗原表型方面已广泛发展。然而,尽管有很大的压力要摆脱人类免疫力并在抗原表型上多样化,但H3N2流感在任何时候都显示出自相矛盾的有限的遗传和抗原多样性。在这里,我们提出了一种解释这种明显差异的流感病毒抗原进化的简单模型。结果在该模型中,抗原表型由N维向量表示,病毒突变扰乱了该连续欧几里德空间内的表型。我们在大规模的基于个体的仿真中实现了该模型,并在此过程中发现了模型行为与观察到的流感动态之间的显着对应。该模型显示出快速的进化,但多样性低,同时也说明了该病毒显示的流行病学,遗传,抗原和地理模式。我们发现,从现有人类免疫力的进化会导致流感病毒的快速种群更新,并且这种种群更新主要发生在单个抗原轴上。结论选择性动力学诱导了一条运河化的进化轨迹,其中流感人群的进化命运令人惊讶地可重复。在该模型中,流感人群显示了1到2年的可重复性时间尺度,这表明从理论上可以预测进化动态的窗口。

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