Stochastic Modeling and Simulation of Viral Evolution

被引:0
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作者
Luiza Guimarães Fabreti
Diogo Castro
Bruno Gorzoni
Luiz Mario Ramos Janini
Fernando Antoneli
机构
[1] Universidade Federal de São Paulo,Programa de Pós
[2] Universidade Federal de São Paulo,Graduação em Infectologia
[3] Universidade Federal de São Paulo,Departamentos de Microbiologia, Imunologia, Parasitologia and Medicina, Laboratório de Retrovirologia
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关键词
Viral evolution; Quasispecies theory; Branching process; Lethal mutagenesis; Mutational meltdown; Stochastic simulation;
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摘要
RNA viruses comprise vast populations of closely related, but highly genetically diverse, entities known as quasispecies. Understanding the mechanisms by which this extreme diversity is generated and maintained is fundamental when approaching viral persistence and pathobiology in infected hosts. In this paper, we access quasispecies theory through a mathematical model based on the theory of multitype branching processes, to better understand the roles of mechanisms resulting in viral diversity, persistence and extinction. We accomplish this understanding by a combination of computational simulations and the theoretical analysis of the model. In order to perform the simulations, we have implemented the mathematical model into a computational platform capable of running simulations and presenting the results in a graphical format in real time. Among other things, we show that the establishment of virus populations may display four distinct regimes from its introduction into new hosts until achieving equilibrium or undergoing extinction. Also, we were able to simulate different fitness distributions representing distinct environments within a host which could either be favorable or hostile to the viral success. We addressed the most used mechanisms for explaining the extinction of RNA virus populations called lethal mutagenesis and mutational meltdown. We were able to demonstrate a correspondence between these two mechanisms implying the existence of a unifying principle leading to the extinction of RNA viruses.
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页码:1031 / 1069
页数:38
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