Abstract
Primary monocytes are refractory to HIV-1 infection and become permissive upon differentiation into monocyte-derived dendritic cells (MDDCs) or macrophages. Multiple mechanisms have been proposed to interpret HIV-1 restriction in monocytes. Human cellular miRNAs can modulate HIV-1 infection by targeting either conserved regions of the HIV-1 genome or host gene transcripts. We have recently reported that the translation of host protein pur-alpha is repressed by abundant cellular miRNAs to inhibit HIV-1 infection in monocytes. Here, we report that the transcript of another cellular factor, VprBP [Vpr (HIV-1)-binding protein], was repressed by cellular miRNA-1236, which contributes to HIV-1 restriction in monocytes. Transfection of miR-1236 inhibitors enhanced translation of VprBP in monocytes and significantly promoted viral infection; exogenous input of synthesized miR-1236 mimics into MDDCs suppressed translation of VprBP, and, accordingly, significantly impaired viral infection. Our data emphasize the role of miRNA in modulating differentiation-dependent susceptibility of the host cell to HIV-1 infection. Understanding the modulation of HIV-1 infection by cellular miRNAs may provide key small RNAs or the identification of new important protein targets regulated by miRNAs for the development of antiviral strategies.
Highlights
MiRNAs are small non-coding RNA molecules (18–22 nucleotides) found in eukaryotic cells. miRNAs are vital posttranscriptional regulators, and the binding of miRNAs to the 39untranslated regions on target mRNA transcripts usually results in translational repression or target degradation [1]
We investigated the importance of host factor VprBP in HIV-1 infection
HIV-1 depends on host-cell-encoded factors for completing its life cycle, and hundreds of HIV-1-dependent host genes for replication have been uncovered by uniformly conducted in HIV1 non-natural biology target cells or cell lines [45,46,47]
Summary
MiRNAs are small non-coding RNA molecules (18–22 nucleotides) found in eukaryotic cells. miRNAs are vital posttranscriptional regulators, and the binding of miRNAs to the 39untranslated regions on target mRNA transcripts usually results in translational repression or target degradation [1]. MiRNAs are small non-coding RNA molecules (18–22 nucleotides) found in eukaryotic cells. MiRNAs are vital posttranscriptional regulators, and the binding of miRNAs to the 39untranslated regions on target mRNA transcripts usually results in translational repression or target degradation [1]. Host cellular miRNAs can modulate HIV-1 infection by targeting either the conserved regions of HIV-1 genome or host gene transcripts, and these miRNAs may play pivotal roles in maintaining viral latency and promoting host defense [12,13,14]. HIV-1 nef appears to be the most widely focused gene for studying binding with miRNAs. The highly expressed cellular miRNAs miR-125b, miR-150, miR-28, miR-
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