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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3' Untranslated Regions / genetics
-
Carrier Proteins / biosynthesis
-
Carrier Proteins / genetics
-
Carrier Proteins / physiology*
-
Cell Differentiation
-
Cells, Cultured
-
Dendritic Cells / cytology
-
Dendritic Cells / virology
-
Gene Expression Regulation / genetics*
-
Gene Knockdown Techniques
-
Genes, Reporter
-
Genetic Vectors
-
HEK293 Cells
-
HIV-1 / physiology*
-
Host Specificity
-
Host-Pathogen Interactions
-
Humans
-
MicroRNAs / agonists
-
MicroRNAs / antagonists & inhibitors
-
MicroRNAs / physiology*
-
Monocytes / metabolism
-
Monocytes / virology*
-
Protein Biosynthesis / genetics*
-
Protein Serine-Threonine Kinases
-
RNA, Small Interfering / pharmacology
-
Transfection
-
Ubiquitin-Protein Ligases
Substances
-
3' Untranslated Regions
-
Carrier Proteins
-
MIRN1236 microRNA, human
-
MicroRNAs
-
RNA, Small Interfering
-
Ubiquitin-Protein Ligases
-
DCAF1 protein, human
-
Protein Serine-Threonine Kinases
Grants and funding
This work was supported by grants to J.H.W. from the Interdisciplinary and Collaboration team of Chinese Academy of Sciences; the Natural Science Foundation of China (No. 81171567), and the National Basic Research Program of China (973 Program) (2012CB519004). J.H.W. gratefully acknowledges the support of the Sanofi-Aventis-SIBS Scholarship Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.