Cocaine enhances HIV-1 infectivity in monocyte derived dendritic cells by suppressing microRNA-155

PLoS One. 2013 Dec 31;8(12):e83682. doi: 10.1371/journal.pone.0083682. eCollection 2013.


Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Cocaine / pharmacology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / virology*
  • Dopamine Uptake Inhibitors / pharmacology
  • Flow Cytometry
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / virology*
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Virus Replication / drug effects*


  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Dopamine Uptake Inhibitors
  • Lectins, C-Type
  • MIRN155 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Luciferases
  • Cocaine