Analyses of paired host-virus genomic data to understand disease heterogeneity of chronic viral infections. (360G-Wellcome-220171_Z_20_Z)

Host and pathogen genetic variations are major causes of clinical outcomes of infectious diseases. Traditionally, genetic studies of infectious diseases have sought to explain between-individual variation in disease by assessing genetic factors separately in humans or pathogens, under the assumption that these factors are independent. However, there is strong theoretical evidence that genetic interactions between host and viruses play a major role in viral disease aetiology. The major limiting factor to date has been the lack of cohorts with paired host-virus data. Recent technological developments and reductions in the cost of high-throughput viral sequencing from clinical samples have provided new opportunities to analyse host-virus genomic data generated from the same patients. In this project I propose to analyse paired host-virus genomic data from patient cohorts infected with HBV, HCV and HIV (clinically the most important chronic viruses worldwide) to answer the following questions: 1) What are the host genetic pressures driving virus evolution across different host populations and virus lineages? 2) What host and virus genetic interactions drive disease phenotypes? 3) What are the host genetic variants and pathways linked to disease phenotype across the three chronic viral infections of HBV, HCV and HIV?