Fate of Invisible U/A Pairs Within HIV DNA in Cells of the Myeloid Phagocytic System

We seek to understand how uracilation impacts infection of three types of cells of the myeloid phagocytic system: alveolar macrophages (AMs) present in bronchial alveolar lavage (BAL) samples, in vitro differentiated MDMs (ivd-MDMs), and peripheral blood MCs. The role of uracilation and UBER in generating proviral genetic diversity, lethal viral mutations, restoration of coding T/A pairs, and viral persistence by uracil-induced silencing will be determined. We will then test whether the sequences of proviral DNA detected in rare circulating monocytes of aviremic patients on long-term retroviral therapy (cART) report on a persistent pool of latent uracilated viruses residing in tissue macrophages.