On state-space reduction in multi-strain pathogen models, with an application to antigenic drift in influenza A.
On state-space reduction in multi-strain pathogen models, with an application to antigenic drift in influenza A.
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DOI：
10.1371/journal.pcbi.0030159
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发表时间：
2007-08
影响因子：
4.3
通讯作者：
Dushoff, Jonathan
中科院分区：
文献类型：
--
作者：
Kryazhimskiy, Sergey;Dieckmann, Ulf;Levin, Simon A.;Dushoff, Jonathan
许多病原体存在于表型不同的菌株中，这些菌株通过竞争宿主而相互作用。描述此类多应变系统的通用模型极难分析，因为它们的状态空间非常大。简化模型已经被提出，但到目前为止，所有这些模型都必然允许同时感染，并要求免疫仅通过降低传染性来介导，这是一个潜在有问题的假设。在这里，我们提出了一种新的状态空间缩减方法，该方法允许通过降低传染性或降低易感性来介导免疫力，并且自然可以用于有或没有合并感染的模型。我们的方法利用基于状态的模型的总体框架。我们方法的基石是引入免疫变量，它比传统的易感和感染宿主跟踪更自然地描述多菌株系统。以这种方式表达的模型可以通过类似于矩闭包的截断方法以自然的方式逼近，使我们能够急剧减小状态空间的大小，从而以易于处理的方式考虑具有许多应变的模型。将我们的方法应用于甲型流感抗原漂移现象，我们提出了一种潜在的通用机制，可以将病毒进化限制为二维特征空间中的一维流形。我们的框架拓宽了多菌株系统的类别，可以通过简化模型充分描述。它允许计算甚至分析研究，因此可以作为了解多菌株病原体的进化和生态学的有用工具。许多重要的人类病原体，包括艾滋病毒和流感病毒，由许多不同的“毒株”组成，这些“毒株”会在宿主体内引发不同的免疫反应。一种变体的感染通常会引发针对其他几种变体的部分交叉免疫。这个过程导致宿主群体中形成复杂且动态的免疫结构。大多数现有的多菌株病原体群体模型要么非常复杂，要么依赖于特定的简化假设。在这里，我们提出了一种简化此类模型的新方法，该方法可以使基本假设具有更大的灵活性。这种方法可以使人们更深入地了解多菌株病原体的生态和进化。我们将我们的方法应用于甲型流感进化的简单模型，该模型说明了有关甲型流感进化如何构建的一个假设。
Many pathogens exist in phenotypically distinct strains that interact with each other through competition for hosts. General models that describe such multi-strain systems are extremely difficult to analyze because their state spaces are enormously large. Reduced models have been proposed, but so far all of them necessarily allow for coinfections and require that immunity be mediated solely by reduced infectivity, a potentially problematic assumption. Here, we suggest a new state-space reduction approach that allows immunity to be mediated by either reduced infectivity or reduced susceptibility and that can naturally be used for models with or without coinfections. Our approach utilizes the general framework of status-based models. The cornerstone of our method is the introduction of immunity variables, which describe multi-strain systems more naturally than the traditional tracking of susceptible and infected hosts. Models expressed in this way can be approximated in a natural way by a truncation method that is akin to moment closure, allowing us to sharply reduce the size of the state space, and thus to consider models with many strains in a tractable manner. Applying our method to the phenomenon of antigenic drift in influenza A, we propose a potentially general mechanism that could constrain viral evolution to a one-dimensional manifold in a two-dimensional trait space. Our framework broadens the class of multi-strain systems that can be adequately described by reduced models. It permits computational, and even analytical, investigation and thus serves as a useful tool for understanding the evolution and ecology of multi-strain pathogens. Many important human pathogens, including HIV and influenza viruses, consist of many different “strains,” which elicit distinct immune responses in their hosts. Infection by one variant usually triggers partial cross-immunity against several other variants. This process leads to a complicated and dynamic immunity structure in the host population. Most existing models of a population with a multi-strain pathogen are either very complex, or rely on specific simplifying assumptions. Here, we suggest a new way of simplifying such models that allows for greater flexibility in underlying assumptions. This approach could lead to deeper understanding of the ecology and evolution of multi-strain pathogens. We apply our approach to a simple model of evolution of influenza A that illustrates one hypothesis about how influenza A evolution may be structured.
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影响因子：
2
作者：
Lin, J;Andreasen, V;Levin, SA
通讯作者：
Levin, SA
影响因子：
56.9
作者：
Gupta, S;Ferguson, N;Anderson, R
通讯作者：
Anderson, R
影响因子：
64.8
作者：
Ferguson, NM;Galvani, AP;Bush, RM
通讯作者：
Bush, RM
影响因子：
1.9
作者：
Andreasen, V;Lin, J;Levin, SA
通讯作者：
Levin, SA
DOI：
10.1073/pnas.252512799
发表时间：
2002-12-24
影响因子：
11.1
作者：
Gog, JR;Grenfell, BT
通讯作者：
Grenfell, BT