The Long Noncoding RNAHEALRegulates HIV-1 Replication through Epigenetic Regulation of the HIV-1 Promoter

Despite our increased understanding of the functions of lncRNAs, their potential to develop HIV/AIDS cure strategies remains unexplored. A genome-wide analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs) was performed, and 1,145 differentially expressed lncRNAs were identified. An lncRNA namedHIV-1-enhancedlncRNA (HEAL) is upregulated by HIV-1 infection and promotes HIV replication in T cells and macrophages.HEALforms a complex with the RNA-binding protein FUS to enhance transcriptional coactivator p300 recruitment to the HIV promoter. Furthermore,HEALknockdown and knockout prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment, suggestingHEALas a potential therapeutic target to cure HIV-1/AIDS.