The impact of virus genetics on transmissibility of HIV-1 (360G-Wellcome-201355_Z_16_Z)

Genome-wide association studies (GWAS) have greatly improved our understanding of human disease genetics, and are beginning to be applied to pathogens. Current pathogen GWAS have largely focused on the identification of variants behind bacteria and parasite drug resistance. A neglected application is identifying variants determining infectiousness for viruses such as HIV-1. HIV transmission is influenced in large part by an individual’s set point viral load (spVL), which itself is determined by variation in the viral genome. Given HIV’s short genome and large amount of common genetic diversity, spVL provides a tractable target in terms of potential pathogen GWAS with large global health implications. During this fellowship I will first adapt GWAS to HIV whole genome sequences by focusing on drug resistance, a phenotype where many variants are already well understood. Once the methods are perfected, I will analyse spVL in the PANGEA_HIV sample of 20,000 whole genome sequences. Identified variants will be combined with demographic data to understand how they influence transmission on a population level. They will also be tested for interactions with host genetic variants, to understand the biology of immune escape. This will allow for a better understanding of transmission risk.