HIV-1 adaptation to HLA: a window into virus–host immune interactions

• Human leukocyte antigen (HLA) class I-restricted immune responses exert strong selection pressures on HIV-1, driving viral evolution through immune escape.
• The mutational pathways and time-course of HIV-1 immune escape are specific and reproducible in the context of host HLA class I alleles.
• Viral diversity and immune escape are barriers to sustained host control of HIV-1 and the design of effective HIV-1 vaccines.
• Study of HLA-driven viral adaptation has yielded important insights that can be harnessed into HIV vaccine design strategies.

HIV-1 develops specific mutations within its genome that allow it to escape detection by human leukocyte antigen (HLA) class I-restricted immune responses, notably those of CD8+ cytotoxic T lymphocytes (CTL). HLA thus represents a major force driving the evolution and diversification of HIV-1 within individuals and at the population level. Importantly, the study of HIV-1 adaptation to HLA also represents an opportunity to identify what qualities constitute an effective immune response, how the virus in turn adapts to these pressures, and how we may harness this information to design HIV-1 vaccines that stimulate effective cellular immunity.