EVOLUTIONARY INFERENCES OF INFLUENZA VIRUSES BY PHYLOGENETIC ENGINEERING

Abstract

Influenza is an infectious respiratory disease in humans. Human-adapted influenza viruses cause recurring seasonal epidemics due to antigenic drift. Sporadic zoonoses of non-human influenza strains can potentially lead to global pandemics of severe public health consequences. As such, influenza viruses are among the most monitored pathogens worldwide. This thesis uses publicly available sequences and corresponding meta-information derived from global surveillance efforts, employs phylogenetic reconstruction and newly developed methods to gain insights into the evolution of seasonal and pandemic influenza viruses. Chapter 2 investigates the role of individual level selection pressure on the antigenic evolution of seasonal influenza viruses. Chapter 3 details the development of PhyCLIP, a statistically-principled phylogenetic clustering algorithm that minimise the arbitrariness commonly inherent in the divergence thresholds underlying pathogen nomenclature systems. Chapter 4 uses Sequence Harmony, an information-centric methodology to identify putative, naturally-occurring human adaptive mutations on the polymerase basic 2 gene segment of avian influenza viruses.