Cellular metabolism plays a critical role in regulating T-cell immunity. T cell functions, such as proliferation, secretion of cytokines and cell survival, are supported through different engagement of metabolic pathways. We have found that HIV exploits the metabolic requirements of CD4+ T-cells to establish infection, identifying a vulnerability to target the infected cells. On the other hand, we have observed that while natural HIV controllers establish optimal HIV-specific CD8+ T-cell memory characterized by metabolic plasticity, non-controllers have skewed memory responses with strict glucose dependency. Interestingly, metabolic reprogramming of CD8+ T cells from non-controllers can enhance their antiviral potential. Overall, our results establish a link between cell metabolism and both HIV-specific CD8+ T-cell functionality and the establishment and persistence of CD4+ T-cell reservoirs and may provide valuable leads to tackle HIV infection.
This work was conducted with funds from ANRS, MSDAVENIR, amfAR, Sidaction and from the European Union (EU)’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 706871.