Potentiating host immuno-metabolism as a novel approach toward reservoir eradication and functional cure in HIV-1 infection

Human Immunodeficiency Virus type 1 (HIV-1) persists in long-lived infected cells that are not affected by antiretroviral treatment (ART) and the barrier to the functional HIV-cure.

Our recent studies, preliminary data, and others indicated that targeting the immune-metabolic pathways towards central carbon metabolism (CCM) is a potential therapeutic tool to modulate immune response with the hope to clear HIV from reservoirs.

We aim to apply computer-driven genome-scale metabolic models (GSMM) to the transcriptomics data from long-term successfully treated cohorts to characterize the metabolic and signaling rearrangement of host cells upon HIV-1 persistence (Aim#1).

Further we will perform single-cell metabolic analysis, immune phenotyping and RNAflow based reservoir quantification on the patient materials to understand the diverse metabolic state associated with the latent viral reservoir (Aim#2).

Finally we will modulate CCM in an ex vivo primary latent cell model and in vivo latency mouse models to understand the metabolic modulation of HIV-persistence (Aim#3).

Our study thus uses a novel approach to delineate the possibility of utilizing immunometabolism as a new target towards HIV-1 management and cure that allow a fruitful route to the computational guiding of experimental HIV-reservoir eradication strategies.

Detailed metabolic mapping of the well-treated individuals and its association with the HIV-reservoir can provide novel direction towards HIV-cure strategies.