Cytolytic CD4 T cell-mediated viral selection pressure: Defining potential strategies for therapeutic and prophylactic HIV vaccines (B09)

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The role of CD4 T cells in the control of chronic viral infections is well established. Besides helper functions for CD8 T cells and B cells, non-traditional CD4 T cell functions have been implicated to significantly contribute to the control of viral infections including influenza, HBV and HIV. In this grant proposal we plan to determine 1.) the mechanisms involved in the induction of CD4 T cell-mediated cytotoxicity, 2.) the properties of the synapse formation and cytolytic pathways of CD4 T cells as well as the influence of inhibitory receptors on the synapse formation and 3.) we will reveal genetic regions of cytolytic CD4 T cell immune selection in the virus sequence and the consequence of these mutations on viral fitness. Overall, this grant proposal is designed to determine the mechanisms of cytolytic induction and function of CD4 T cells and their contribution to viral evolution and selection pressure in chronic HIV infection.