From molecules to pandemics: multi-level adaptation of human chronic viruses. (360G-Wellcome-107652_Z_15_Z)

Chronic viruses, such as HIV and HCV, evolve rapidly within individuals. Combined with long durations of infection, this means transmitted strains will be different from founder strain(s) that initiate infections, which in turn will have large effects on these viruses at the epidemiological scale including: the rate of spread of transmitted drug resistance; adaptation to the HLA background of the host population; and the evolution of viral pathogenesis. I will determine how virus evolution withi n-hosts affects the epidemiology of chronic viruses and predict the consequences of these effects under different intervention scenarios. It is becoming increasingly apparent that the presence of viral reservoirs and compartmentalisation has qualitative effects on within-host viral evolution. I will fit mathematical models to next-generation sequencing data to establish whether this significantly delays within-host evolutionary dynamics in natural and drug treated infections, and whether vir al strains similar to founder strains are preferentially transmitted. Importantly, I will test whether we see the same patterns for different classes of mutations, such as immune and drug escape mutations. This will allow me to develop epidemiological models that integrate within-host and transmission processes and ask how this impacts the among-host evolution of chronic viral infections.