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.

本研究旨在阐明尿嘧啶化（uracilation）对髓系吞噬细胞系统三类细胞感染过程的影响：支气管肺泡灌洗液（BAL）样本中的肺泡巨噬细胞（AMs）、体外分化单核细胞衍生巨噬细胞（ivd-MDMs），以及外周血单核细胞（MCs）。本研究将明确尿嘧啶化（uracilation）与UBER在介导前病毒遗传多样性生成、诱导致死性病毒突变、修复编码区域的T/A碱基对，以及通过尿嘧啶诱导的沉默作用维持病毒持久性过程中的作用。随后，本研究将检验接受长期联合抗逆转录病毒治疗（cART）的无病毒血症患者的稀有循环单核细胞中检出的前病毒DNA（proviral DNA）序列，是否能够反映驻留于组织巨噬细胞中的潜伏尿嘧啶化病毒持续储存库。