The evolutionary and mechanistic basis of virus host shifts. (360G-Wellcome-109356_Z_15_Z)

Despite host shifts being a major source of emerging infectious disease, we have much to learn about why hosts vary in their susceptibilities to novel pathogens and how viruses evolve in new hosts. The first goal of this fellowship is to understand what factors affect the ability of a virus to infect a novel host. I will break the infection process down into different steps to test whether differences in susceptibility are due to the ability of the virus to: bind, enter, replicate in, and exit h ost cells. I will then examine whether the ability of the virus to suppress the host immune response can determine whether it can infect novel hosts. I will investigate the relative importance of environmental versus host-genetic factors in determining the success of host shifts by determining how susceptibility changes with temperature. Next I will use viruses experimentally evolved in different species to examine how viruses adapt to host species, and what consequences this has on their abilit y to infect further hosts. Finally, I will evolve viruses in alternating hosts, using closely or distantly related species, to examine how host breadth affects the potential of a virus to infect a range of novel hosts.