title: The inhibition of microRNAs by HIV-1 Tat suppresses beta catenin activity in astrocytes.
abstract: BACKGROUND
  Long term infection with HIV-1, even in the context of therapy, leads to chronic health problems including an array of neurocognitive dysfunctions. The viral Tat protein has previously been implicated in neuropathogenesis through its effect on astrocytes. Tat has also been shown to inhibit the biogenesis of miRNAs by inhibiting the activity of the cellular Dicer protein in an RNA dependent fashion. Whether there is a mechanistic connection between the ability of HIV-1 Tat to alter miRNAs and its observed effects on cells of the central nervous system has not been well examined.
  
  
  RESULTS
  Here, we examined the ability of HIV-1 Tat to bind to and inhibit the production of over 300 cellular miRNAs. We found that the Tat protein only binds to and inhibits a fraction of the total cellular miRNAs. By mapping the downstream targets of these miRNAs we have determined a possible role for Tat alterations of miRNAs in the development of neuropathogenesis. Specifically, this work points to suppression of miRNAs function as the mechanism for Tat suppression of β-catenin activity.
  
  
  CONCLUSIONS
  The discovery that HIV-1 Tat inhibits only a fraction of miRNAs opens new areas of research regarding changes in cellular pathways through suppression of RNA interference. Our initial analysis strongly suggests that these pathways may contribute to HIV-1 disruption of the central nervous system.
authors.affiliation: Department of Biological Sciences, McNeil Science and Technology Center Room 273, University of the Sciences, 600 S 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Sardo
authors.affiliation: Department of Biological Sciences, McNeil Science and Technology Center Room 273, University of the Sciences, 600 S 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Priyal R
authors.initials: PR
authors.lastname: Vakil
authors.affiliation: Department of Biological Sciences, McNeil Science and Technology Center Room 273, University of the Sciences, 600 S 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Weam
authors.initials: W
authors.lastname: Elbezanti
authors.affiliation: Department of Biological Sciences, McNeil Science and Technology Center Room 273, University of the Sciences, 600 S 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Anas
authors.initials: A
authors.lastname: El-Sayed
authors.affiliation: Department of Biological Sciences, McNeil Science and Technology Center Room 273, University of the Sciences, 600 S 43rd Street, Philadelphia, PA, 19104, USA. z.klase@usciences.edu.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Klase
mesh_terms: D001253:Astrocytes / Q000821:virology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D016601:RNA-Binding Proteins; D051176:beta Catenin; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: Astrocyte; Beta-catenin; HAND; HIV-1; Tat; miRNA