Stochastic Modeling and Simulation of Viral Evolution

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 phenotypic model, to better understand the roles of mechanisms resulting in viral diversity, persistence and extinction. We accomplished this by a combination of computational simulations and the application of analytic techniques based on the theory of multitype branching processes. In order to perform the simulations we have implemented the phenotypic 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 virus populations may display four distinct regimes from its introduction to 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. keywords: Viral evolution, Quasispecies theory, Multitype branching process, Lethal mutagenesis, Mutational meltdown 1Programa de Pós-Graduação em Infectologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil. 2Departamentos de Microbiologia, Imunologia, Parasitologia and Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. 3Departamento de Informática em Saúde and Laboratório de Biocomplexidade e Genômica Evolutiva, Universidade Federal de São Paulo, São Paulo, SP, Brazil. ∗Corresponding author. E-mail: [email protected] 1 ar X iv :1 70 6. 04 64 0v 2 [ qbi o. PE ] 1 0 N ov 2 01 7