The evolutionary and mechanistic basis of virus host shifts - A Staphylococcaceae-phage system to investigate patterns of virus infectivity and evolution across host species

Abstract

Virus host shifts are a major source of emerging infectious diseases, resulting in both epidemics and pandemics which cause substantial damage to both public health and the global economy. The considerable societal and economic costs of virus host shifts have made understanding the underlying factors that contribute to these events, and how we may best predict and prevent them, a major goal of infectious disease research. In this thesis, I established an experimentally tractable bacteria-bacteriophage model system for the investigation of virus host shifts and used it to investigate several questions relating to the evolutionary and molecular determinants of host shifts: whether the evolutionary relationships between hosts can explain variation in their susceptibility to infection with a virus; how adaptation of a virus to a host influences its ability to infect subsequent hosts; and whether in vitro measures of host susceptibility to viral infection correlate with in vivo measures of susceptibility. The system comprises of a large and phylogenetically diverse panel of Staphylococcaceae bacteria, spanning approximately 112 million years of evolutionary history, and the dsDNA bacteriophage ISP, which is currently under investigation for use in phage therapy.