title: HIV-1 gp120 influences the expression of microRNAs in human monocyte-derived dendritic cells via STAT3 activation.
abstract: BACKGROUND
  MicroRNAs (miRs) are an abundant class of small non-coding RNAs (~22 nt) that reprogram gene expression by targeting mRNA degradation and translational disruption. An emerging concept implicates miR coupling with transcription factors in myeloid cell development and function, thus contributing to host defense and inflammation. The important role that these molecules play in the pathogenesis of HIV-1 is only now emerging.
  
  
  RESULTS
  We provide evidence that exposure of monocyte-derived dendritic cells (MDDCs) to recombinant HIV-1 R5 gp120, but not to CCR5 natural ligand CCL4, influences the expression of a panel of miRs (i.e., miR-21, miR-155 and miR-181b) regulated by STAT3 and potentially targeting genes belonging to the STAT3 signaling pathway. The blockage of gp120-induced STAT3 activation impairs gp120 capacity to modulate the expression level of above mentioned miRs. Predictive analysis of miR putative targets emphasizes that these miRs share common target genes. Furthermore, gene ontology and pathway enrichment analysis outline that these genes mainly belong to biological processes related to regulation of transcription, in a complex network of interactions involving pathways relevant to HIV-DC interaction.
  
  
  CONCLUSIONS
  Overall, these results point to gp120-triggered modulation of miR expression via STAT3 activation as a novel molecular mechanism exploited by HIV-1 to affect DC biology and thus modulate the immune response through complex regulatory loops involving, at the same time, miRs and transcription factors.
authors.affiliation: Bambino Gesù Children's Hospital-IRCCS, Viale di San Paolo 15, 00146, Rome, Italy. andrea.masotti@opbg.net.
authors.forename: Andrea
authors.initials: A
authors.lastname: Masotti
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. gloria.donninelli@iss.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Donninelli
authors.affiliation: Bambino Gesù Children's Hospital-IRCCS, Viale di San Paolo 15, 00146, Rome, Italy. letizia.dasacco@opbg.net.
authors.forename: Letizia
authors.initials: L
authors.lastname: Da Sacco
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. barbara.varano@iss.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Varano
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. manuela.delcorno@iss.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Del Cornò
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. sandra.gessani@iss.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gessani
mesh_terms: D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D015870:Gene Expression / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015699:HIV Envelope Protein gp120; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human