Grant: Doctoral Research Award - PA: Biomedical/Clinical HIV/AIDS Research

Human immunodeficiency virus type-1 (HIV-1) is the primary cause of acquired immunodeficiency syndrome (AIDS) and is one of the 3 greatest infectious disease killers globally. Some people appear to be resistant to HIV infection, remaining uninfected despite exposure. Among those who become infected a small subset of about 5% progress slowly without treatment. There is epidemiological evidence that Natural Killer (NK) cells, through interactions between certain NK receptors (KIR3DL1) and their ligands (HLA-Bw4), play a role in HIV resistance as well as slow disease progression in infected subjects. In this project I will work with cells from HIV exposed uninfected individuals typed for KIR3DL1 and HLA-Bw4 and study the linkage between the anti-viral function of NK cells from individuals having KIR/HLA receptor ligand pairs that are associated or not with favorable outcomes following exposure to HIV. In particular I will investigate the ability of NK cells to kill cells after they detect changes that occur on the surface of HIV infected cells. This proposal will contribute to improving our understanding of the role of NK cells in protection from HIV observed in HIV resistant and/or slow disease progressors. Such information would be relevant to vaccine design by providing a rationale for modulating NK activity at the time of vaccination to favor the development of protective immunity.