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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.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC4007588 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Yijun Y   Fan Miaomiao M   Geng Guannan G   Liu Bingfeng B   Huang Zhuoqiong Z   Luo Haihua H   Zhou Jie J   Guo Xuemin X   Cai Weiping W   Zhang Hui H  

Retrovirology 20140312


<h4>Background</h4>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.<h4>Results</h4>In this report, through a strategy combining computational prediction and deep sequencing, we identified a novel HIV-1-encoded miR  ...[more]

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