HIV adaptation to immune selection pressures: historic trends and future implications
HIV has tremendous capacity to mutate and evolve due to the body’s immune response. However, the extent to which the virus has adapted to its human hosts over the course of the pandemic remains poorly understood. Repeated cycles of immune selection and transmission may allow the accumulation of key “escape mutations” — changes in the viral genome that help HIV evade the body’s defences. If immune targets in the HIV genome were disappearing over time due to the accumulation of these mutations, our ability to generate natural and vaccine-induced protective immune responses would diminish as the epidemic progresses.
Furthermore, the extent to which immune escape has influenced HIV pathogenesis remains unknown. Studies investigating the evolution of HIV virulence have largely focused on population-level trends in clinical markers over time, but few have addressed this issue using biological assessments of replication capacity or viral protein function.
Dr. Zabrina Brumme’s research team will undertake the first large-scale investigation of immune-driven HIV evolution and its implications over the 30-year history of the epidemic in North America. Host and viral genetic sequences from 1979 to the present will be analyzed to characterize the extent of population-level HIV adaptation over the epidemic’s course. Functional assessments of viral replication capacity and protein function will be performed to determine whether HIV is evolving towards increased virulence, gradual attenuation, or simply adapting to changing host-pathogen pressures over time.
With this study, Brumme is poised to answer two key questions of HIV biomedical research, namely, to what extent the virus has adapted to its hosts since AIDS was first recognized, and what implications this has for the future of the epidemic. Results have the potential to significantly advance HIV vaccine research.