Ecological and immunological determinants of influenza evolution
Ecological and immunological determinants of influenza evolution
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DOI：
10.1038/nature01509
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发表时间：
2003-03-27
期刊：
影响因子：
64.8
通讯作者：
Bush, RM
中科院分区：
文献类型：
--
作者：
Ferguson, NM;Galvani, AP;Bush, RM
流感以大流行和流行的形式，导致大量的、有时是灾难性的发病和死亡。来自宿主免疫系统的强烈选择驱动甲型和乙型流感的抗原变化，导致流行毒株不断被能够再次感染对早期类型有免疫力的宿主的新变异株所取代。这种“抗原漂移”（1）往往需要在每次年度流行前配制新的疫苗。然而，鉴于流感的高传播性和突变率，随着时间推移，谱系内基因多样性的稳定性是矛盾的。另一个谜团是在由“抗原转变”——一种新的甲型禽流感亚型传入人类群体（1）所导致的全球大流行期间现有毒株的更替。在这里，我们使用一个数学模型来探索这些模式背后的生态和免疫因素，该模型在序列水平上捕捉现实的流行病学动态和病毒进化。通过将模型输出与通过全球监测（2）收集的序列数据中所见的系统发育模式相匹配，我们发现短期的跨毒株免疫力对于限制宿主群体中的病毒多样性以及解释漂移和转变动态的关键方面至关重要。
In pandemic and epidemic forms, influenza causes substantial, sometimes catastrophic, morbidity and mortality. Intense selection from the host immune system drives antigenic change in influenza A and B, resulting in continuous replacement of circulating strains with new variants able to re-infect hosts immune to earlier types. This 'antigenic drift'(1) often requires a new vaccine to be formulated before each annual epidemic. However, given the high transmissibility and mutation rate of influenza, the constancy of genetic diversity within lineages over time is paradoxical. Another enigma is the replacement of existing strains during a global pandemic caused by 'antigenic shift'-the introduction of a new avian influenza A subtype into the human population(1). Here we explore ecological and immunological factors underlying these patterns using a mathematical model capturing both realistic epidemiological dynamics and viral evolution at the sequence level. By matching model output to phylogenetic patterns seen in sequence data collected through global surveillance(2), we find that short-lived strain-transcending immunity is essential to restrict viral diversity in the host population and thus to explain key aspects of drift and shift dynamics.