Phylodynamic Patterns in Pathogen Ecology and Evolution.

[摘要] The rapid evolution of viral pathogens requires us to consider epidemiological, ecological and evolutionary processes as coupled together and occurring at the same timescale. Rotavirus and influenza account for high levels of morbidity and mortality worldwide and are two important examples of such dynamics. In this work, I investigate the different evolutionary and ecological processes that shape the antigenic structure and phylogenetic characteristics of these two viruses. In the first part of my work, I use a theoretical model of influenza A/H3N2 to identify the relative importance of antigenic novelty, competition between lineages, and changes in the susceptibility of the host population to circulating strains in determining the evolutionary and epidemiological trajectory of the virus. I develop this model further to correspond with patterns of immunity and infection observed in rotavirus, and investigate how reassortment, the swapping of gene segments between viruses, influences the formation and replacement of rotavirus genotypes through immune mediated processes. In the second part of my work, I use a tool (SeasMig), which I developed, to infer alternative stochastically generated migration and mutation events along phylogenetic trees in a Bayesian manner. Using SeasMig, I first show how the seasonality of A/H3N2 influenza incidence corresponds to rates of immigration and emigration of the virus. Subsequently, I tease out the different evolutionary and ecological processes, which drive changes in the US rotavirus population following onset of routine vaccination. My work has implications for identifying likely evolutionary mechanisms, which may lead to reduced vaccine efficacy, and for vaccine strain selection.

[发布机构] University of Michigan

[效力级别] Science (General)

[关键词] phylodynamics rotavirus influenza;Science (General);Science;Bioinformatics