title: Translation of Pur-α is targeted by cellular miRNAs to modulate the differentiation-dependent susceptibility of monocytes to HIV-1 infection.
abstract: The postentry restriction of HIV-1 replication in monocytes can be relieved when they differentiate to dendritic cells (DCs) or macrophages. Multiple mechanisms have been proposed to interpret the differentiation-dependent susceptibility of monocytes to HIV-1 infection, and the absence of host-cell-encoded essential factors for HIV-1 completing the life cycle may provide an explanation. We have analyzed the gene expression profile in monocytes by mRNA microarray and compared it with that of differentiated DCs. We demonstrated that purine-rich element binding protein α (Pur-α), a host-cell-encoded ubiquitous, sequence-specific DNA- and RNA-binding protein, showed inadequate expression in monocytes, and the translation of Pur-α mRNA was repressed by cell-expressed microRNA (miRNA). These Pur-α-targeted miRNAs modulated the differentiation-dependent susceptibility of monocytes/DCs to HIV-1 infection, because rescue of Pur-α expression by transfection of miRNA inhibitors relieved the restriction of HIV-1 infection in monocytes, and ectopic input of miRNA mimics significantly reduced HIV-1 infection of monocyte-derived DCs (MDDCs). Collectively, our data emphasized that inadequate host factors contribute to HIV-1 restriction in monocytes, and cellular miRNAs modulate differentiation-dependent susceptibility of host cells to HIV-1 infection. Elaboration of HIV-1 restriction in host cells facilitates our understanding of viral pathogenesis and the search for a new antiviral strategy.
authors: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Chan-Juan
authors: CJ
authors: Shen
authors: Yan-Hui
authors: YH
authors: Jia
authors: Ren-Rong
authors: RR
authors: Tian
authors: Ming
authors: M
authors: Ding
authors: Chiyu
authors: C
authors: Zhang
authors: Jian-Hua
authors: JH
authors: Wang
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C501130:PURA protein, human; D012333:RNA, Messenger; D014157:Transcription Factors