A novel HIV-1-encoded microRNA enhances its viral replication by targeting the TATA box region

Retrovirology

Hui Zhang¹  Weiping Cai²  Xuemin Guo¹  Jie Zhou¹  Haihua Luo¹  Zhuoqiong Huang¹  Bingfeng Liu¹  Guannan Geng¹  Miaomiao Fan¹  Yijun Zhang¹ 

[1] Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China;Department of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510080, China

关键词: Latency;    Viral replication;    Transcription activation;    TATA box;    Viral miRNA;    HIV-1 viruses;   

Others  :  802441
DOI  :  10.1186/1742-4690-11-23

 received in 2013-11-01, accepted in 2014-02-18,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

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