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

The HIV/AIDS epidemic remains a major challenge for medicine, public health and biomedical research, with >25 million people killed by AIDS throughout the world since 1981. More than 60,000 people are currently living with HIV in Canada, with an increasing portion of HIV infections occurring in young Aboriginal women. Despite the key advances made in the HIV field in the past years, an HIV vaccine does not exist yet and eradication has not been achieved with current antiretroviral therapies. Difficulties in solving HIV epidemics are, in part, related to the fact that HIV infects and persists in a small fraction of CD4+ T-cells, with phenotypic and functional characteristics that are still not clearly understood. Therefore, a better understanding of CD4+ T-cell heterogeneity is imperative to allow the design of successful vaccines and/or cell-targeted eradication strategies. The present proposal will provide an in depth characterization of CD4+ T-cell phenotypic and functional heterogeneity under homeostatic conditions and HIV pathogenesis. Our objective is to characterize the contribution to immunity and HIV pathogenesis of two new memory T-cell subsets expressing the gut homing chemokine receptor CCR6 and markers of Th17 polarization. The proposed studies will provide a new understanding of the functional heterogeneity of Th17 cells in the context of HIV pathogenesis and will identify biomarkers for T-cell subsets fuelling HIV replication/persistence in vivo. This knowledge will be critical for purging HIV reservoirs from discrete T-cell subsets and will identify new targets for the development of drugs that interfere with molecular mechanisms of HIV permissiveness versus resistance in primary T-cells.