title: A novel HIV-1-encoded microRNA enhances its viral replication by targeting the TATA box region.
abstract: BACKGROUND
  A lot of microRNAs (miRNAs) derived from viral genomes have been identified. Many of them play various important roles in virus replication and virus-host interaction. Cellular miRNAs have been shown to participate in the regulation of HIV-1 viral replication, while the role of viral-encoded miRNAs in this process is largely unknown.
  
  
  RESULTS
  In this report, through a strategy combining computational prediction and deep sequencing, we identified a novel HIV-1-encoded miRNA, miR-H3. MiR-H3 locates in the mRNA region encoding the active center of reverse transcriptase (RT) and exhibits high sequence conservation among different subtypes of HIV-1 viruses. Overexpression of miR-H3 increases viral production and the mutations in miR-H3 sequence significantly impair the viral replication of wildtype HIV-1 viruses, suggesting that it is a replication-enhancing miRNA. MiR-H3 upregulates HIV-1 RNA transcription and protein expression. A serial deletion assay suggests that miR-H3 targets HIV-1 5' LTR and upregulates the promoter activity. It interacts with the TATA box in HIV-1 5' LTR and sequence-specifically activates the viral transcription. In addition, chemically-synthesized small RNAs targeting HIV-1 TATA box activate HIV-1 production from resting CD4+ T cells isolated from HIV-1-infected patients on suppressive highly active antiretroviral therapy (HAART).
  
  
  CONCLUSIONS
  We have identified a novel HIV-1-encoded miRNA which specifically enhances viral production and provide a specific method to activate HIV-1 latency.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Fan
authors.forename: Guannan
authors.initials: G
authors.lastname: Geng
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Liu
authors.forename: Zhuoqiong
authors.initials: Z
authors.lastname: Huang
authors.forename: Haihua
authors.initials: H
authors.lastname: Luo
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Xuemin
authors.initials: X
authors.lastname: Guo
authors.forename: Weiping
authors.initials: W
authors.lastname: Cai
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. zhangh92@mail.sysu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D001782:Blood Donors; D015967:Gene Expression Regulation, Viral; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D016385:TATA Box; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase