Stochastic Modeling and Simulation of Viral Evolution

Author(s)

Fabreti, Luiza Guimaraes ^[1] ; Castro, Diogo ^[1] ; Gorzoni, Bruno ^[1] ; Ramos Janini, Luiz Mario ^[2] ; Antoneli, Fernando ^[3]

Affiliation

^[1] Univ Fed Sao Paulo, Programa Posgrad Infectol, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Microbiol Imunol Parasitol & Med, Lab Retrovirol, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Informat Saude, Lab Biocomplexidade & Genom Evolut, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Bulletin of Mathematical Biology; v. 81, n. 4, p. 1031-1069, APR 2019.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 14/13382-1 - Computational modeling of populations of RNA virus and the evolution of their phenotypic diversity
• Grantee: Luiza Guimarães Fabreti
• Support Opportunities: Scholarships in Brazil - Scientific Initiation