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High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Two cellular microRNAs, miR-196b and miR-1290, contribute to HIV-1 latency
Pengfei Wang1, Xiying Qu1, Xin Zhou1
1State Key Laboratory of Genetic Engineering, and Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, School of Life Sciences, Fudan University, Shanghai, China.
Abstract:
Understanding the mechanism of HIV-1 latency is crucial to the viral reservoir eradication. Human cellular miRNAs can modulate HIV-1 expression by targeting of viral RNAs or host gene transcripts. To identify miRNAs modulating HIV-1 latency, we determined the miRNA expression profiles of HIV-1 latently infected and productively infected cells by microarray and qRT-PCR. Among the differentially expressed miRNAs, miR-196b and miR-1290 targeted the 3' untranslated region of HIV-1 and affected its expression. Ectopic expression of these two miRNAs efficiently suppressed HIV-1 production and infectivity. Specific inhibitors of these miRNAs substantially counteracted their effects on HIV-1, as measured either as viral production and infectivity in HEK-293T cells or as HIV-1 RNA expression or viral production in cells isolated from HIV-1-infected individuals. Our study emphasizes the role of cellular miRNAs in HIV-1 latency regulation, and it suggests that inhibitors of miR-196b and miR-1290 could be used to activate latent HIV-1.
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