Exosome-mediated shuttling of microRNA-29 regulates HIV Tat and morphine-mediated neuronal dysfunction

Cell Death Dis. 2012 Aug 30;3(8):e381. doi: 10.1038/cddis.2012.114.


Neuronal damage is a hallmark feature of HIV-associated neurological disorders (HANDs). Opiate drug abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Opiates such as morphine have been shown to enhance HIV transactivation protein Tat-mediated toxicity in both human neurons and neuroblastoma cells. In the present study, we demonstrate reduced expression of the tropic factor platelet-derived growth factor (PDGF)-B with a concomitant increase in miR-29b in the basal ganglia region of the brains of morphine-dependent simian immunodeficiency virus (SIV)-infected macaques compared with the SIV-infected controls. In vitro relevance of these findings was corroborated in cultures of astrocytes exposed to morphine and HIV Tat that led to increased release of miR-29b in exosomes. Subsequent treatment of neuronal SH-SY5Y cell line with exosomes from treated astrocytes resulted in decreased expression of PDGF-B, with a concomitant decrease in viability of neurons. Furthermore, it was shown that PDGF-B was a target for miR-29b as evidenced by the fact that binding of miR-29 to the 3'-untranslated region of PDGF-B mRNA resulted in its translational repression in SH-SY5Y cells. Understanding the regulation of PDGF-B expression may provide insights into the development of potential therapeutic targets for neuronal loss in HIV-1-infected opiate abusers.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Astrocytes / metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Exosomes / metabolism*
  • Ganglia / drug effects
  • Ganglia / metabolism
  • Gene Expression Regulation*
  • Humans
  • Macaca mulatta
  • MicroRNAs / metabolism*
  • Morphine / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Proto-Oncogene Proteins c-sis / genetics
  • Proto-Oncogene Proteins c-sis / metabolism
  • Rats
  • Simian Immunodeficiency Virus / pathogenicity
  • Transfection
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*


  • 3' Untranslated Regions
  • Analgesics, Opioid
  • MIRN29a microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-sis
  • tat Gene Products, Human Immunodeficiency Virus
  • Morphine