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宿主免疫与病原体多样性:一项计算研究。

Host immunity and pathogen diversity: A computational study.

作者信息

Aquino Tomás, Nunes Ana

机构信息

a Department of Civil & Environmental Engineering and Earth Sciences ; University of Notre Dame ; Notre Dame , IN USA.

b BioISI Biosystems & Integrative Sciences Institute and Departamento de Física; Faculdade de Ciências da Universidade de Lisboa ; Lisboa , Portugal.

出版信息

Virulence. 2016;7(2):121-8. doi: 10.1080/21505594.2016.1149284.

Abstract

The distinctive features of human influenza A phylogeny have inspired many mathematical and computational studies of viral infections spreading in a host population, but our understanding of the mechanisms that shape the coupled evolution of host immunity, disease incidence and viral antigenic properties is far from complete. In this paper we explore the epidemiology and the phylogeny of a rapidly mutating pathogen in a host population with a weak immune response, that allows re-infection by the same strain and provides little cross-immunity. We find that mutation generates explosive diversity and that, as diversity grows, the system is driven to a very high prevalence level. This is in stark contrast with the behavior of similar models where mutation gives rise to a large epidemic followed by disease extinction, under the assumption that infection with a strain provides lifelong immunity. For low mutation rates, the behavior of the system shows the main qualitative features of influenza evolution. Our results highlight the importance of heterogeneity in the human immune response for understanding influenza A phenomenology. They are meant as a first step toward computationally affordable, individual based models including more complex host-pathogen interactions.

摘要

甲型流感病毒独特的系统发育特征激发了许多关于病毒感染在宿主群体中传播的数学和计算研究,但我们对塑造宿主免疫、疾病发病率和病毒抗原特性的耦合进化机制的理解还远远不够完善。在本文中,我们探讨了一种快速变异病原体在免疫反应较弱的宿主群体中的流行病学和系统发育情况,这种宿主群体允许同一毒株再次感染,且几乎没有交叉免疫。我们发现,突变会产生爆发性的多样性,而且随着多样性的增加,系统会被驱动到非常高的流行水平。这与类似模型的行为形成了鲜明对比,在假设感染一种毒株可提供终身免疫的情况下,类似模型中突变会引发大规模疫情,随后疾病灭绝。对于低突变率,系统的行为显示出流感进化的主要定性特征。我们的结果强调了人类免疫反应异质性对于理解甲型流感现象的重要性。它们旨在作为迈向计算成本可承受的、基于个体的模型的第一步,该模型包括更复杂的宿主 - 病原体相互作用。

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