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

• DOI: 10.1128/mbio.02016-19
• Publication Date: 2019-09-23T11:35:22Z
• Authors: Ti-Chun Chao; Qiong Zhang; Zhonghan Li; Shashi Kant Tiwari; Yue Qin; Edwin Yau; Ana Sanchez; Gatikrushna Singh; Kungyen Chang; Marcus Kaul; Maile Ann Young K...; Tariq M. Rana
• Keywords: Gene Expression Regulation, Viral; 1.1 Normal biological development and functioning; Immunology; 610; HIV Infections; Virus Replication; Microbiology; epigenetic regulation; Epigenesis, Genetic; Promoter Regions; 03 medical and health sciences; Genetic; Genetics; 2.1 Biological and endogenous factors; Humans; Viral; long noncoding RNAs; Promoter Regions, Genetic; ribonucleoprotein complexes; 0303 health sciences; Biomedical and Clinical Sciences; HIV promoter; Human Genome; Medical microbiology; QR1-502; 3. Good health; Infectious Diseases; Gene Expression Regulation; Medical Microbiology; Biochemistry and cell biology; HIV-1; Sexually Transmitted Infections; HIV/AIDS; RNA; prevention of HIV-1 recrudescence; Long Noncoding; RNA, Long Noncoding; Infection; Epigenesis; Research Article

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.