Grant: Operating Grant

Recent discoveries have shed some light on the mechanisms involved in the pathogenesis of HIV-1/AIDS. Among these, a significant relationship between the depletion by the virus of Th17 cells, which are responsible for the integrity of the intestinal mucosal barrier, and the chronic and systemic immune activation seen in HIV-1-infected patients has been observed. The precise cellular factors involved in the relative susceptibility of these cells compared to others are as yet unknown. Moreover, the discrimination between the genetic program induced in an infected cell compared to another that has been only exposed but not infected, also called bystander cell, has still not been performed. Following the development of a unique and innovative molecular tool allowing the efficient separation of infected from bystander cells, large-scale transcriptomic and proteomic approaches will be used to characterize the gene expression profiles of both infected and bystander cells, identify specific CD4+ T cell subsets that are highly susceptible and others resistant to HIV-1 infection and then determine the exact cellular factors that are responsible for this different susceptibility. These approaches have the potential to provide as-yet unknown targets of intervention for the development of therapies seeking to either prevent HIV-1 transmission, or delay, perhaps indefinitely, the development of AIDS in infected patients.