Phylogenetic Dependency Networks: Inferring patterns of adaptation in HIV

Jonathan M. Carlson One of the enduring challenges facing HIV vaccine design is the remarkable rate of viral mutation and adaptation that limits the ability of the immune system to mount a lasting effective response. This rapid rate of mutation leads to extensive withinand betweenhost viral diversity that makes creation of a broadly reactive vaccine difficult. A first step in overcoming this challenge is to identify consistent patterns in viral adaptation. To this end, this dissertation proposes a new approach to modeling adaptation. This approach is applied to the largest available collection of HIV sequences, taken from chronically infected individuals for whom we also have detailed human genetic data. The result is a detailed prediction of how HIV interacts with, and adapts to, different immune systems, suggesting weak points in HIV's ability to adapt that may provide a window of opportunity for future vaccines.