Investigation of host and viral genetic factors influencing HIV-1 evolution across North America: implications for vaccine design

Human leukocyte antigen (HLA) class I restricted cytotoxic T-lymphocyte (CTL) responses drive HIV-1 evolution through the selection of immune escape mutations, however, the extent to which population-level patterns of immune escape have changed over the course of the HIV-1 epidemic in North America remains incompletely known. The objective of this thesis was to explore how immune selection pressures mediated through host HLA-restricted CTL responses have shaped the genomic and functional evolution of the HIV-1 gag gene over the course of the epidemic in North America. Results support the continued dynamic adaptation of HIV-1 as it passes through human hosts rather than the substantial accumulation of escape mutations over the course of the epidemic in North America. Additionally, only modest increases in gag-mediated replication capacity between pre- and post-1985 sequences were observed. Although the mechanism(s) behind these increases remain unknown, they may be attributable to factors other than CTL-driven immune responses.