title: miRNA-1236 inhibits HIV-1 infection of monocytes by repressing translation of cellular factor VprBP.
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.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology & Medical Sciences, Soochow University, Suzhou, China; Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Shen
authors.affiliation: Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada.
authors.forename: Éric A
authors.initials: ÉA
authors.lastname: Cohen
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology & Medical Sciences, Soochow University, Suzhou, China.
authors.forename: Si-Dong
authors.initials: SD
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology; D005786:Gene Expression Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology*; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D014176:Protein Biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D044767:Ubiquitin-Protein Ligases
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; C571208:MIRN1236 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; C530533:DCAF1 protein, human; D017346:Protein Serine-Threonine Kinases