HIV WGS and Population Diversity Analysis. Human immunodeficiency virus 1

The evolutionary pathways of highly variable pathogens under immune selection pressure remain poorly defined. Here, we applied ultra-deep 454 sequencing along with novel assembly and variant detection algorithms to comprehensively characterize the onset and dynamics of HIV-1 evolution during both acute and chronic infection. Our ability to detect low frequency mutations (<1%) across complete viral genomes revealed previously unappreciated early evolution during the decline in peak viremia. Detailed immunological analyses identified that the majority of these early, low frequency mutations reflected adaptation to CD8+ T cell responses. Moreover, we observed a temporal link between escape from immunodominant CD8 T cell responses and establishment of viral load set point, suggesting that the rate of escape from front-line CD8 T cell responses may strongly influence primary control of HIV-1. Thus, early viral adaptations not detected by conventional sequencing may have a substantial impact upon immune control during acute HIV-1 infection.