title: Effect of μ-opioid agonist DAMGO on surface CXCR4 and HIV-1 replication in TF-1 human bone marrow progenitor cells.
abstract: BACKGROUND
  Approximately one-third of the AIDS cases in the United States have been attributed to the use of injected drugs, frequently involving the abuse of opioids. Consequently, it is critical to address whether opioid use directly contributes to altered susceptibility to HIV-1 beyond the increased risk of exposure. Previous in vitro and in vivo studies addressing the role of μ-opioid agonists in altering levels of the co-receptor CXCR4 and subsequent HIV-1 replication have yielded contrasting results. The bone marrow is believed to be a potential anatomical sanctuary for HIV-1.
  
  
  METHODS
  The well-characterized CD34+CD38+ human bone marrow-derived hematopoietic progenitor cell line TF-1 was used as a model to investigate the effects of the μ-opioid receptor-specific peptide DAMGO (D-Ala2,N-Me-Phe4, Gly5-ol-enkephalin) on CXCR4 expression as well as infection of undifferentiated human hematopoietic progenitor cells.
  
  
  RESULTS
  The results revealed the presence of the μ-opioid receptor-1 isoform (MOR-1) on the surface of TF-1 cells. Furthermore, immunostaining revealed that the majority of TF-1 cells co-express MOR-1 and CXCR4, and a subpopulation of these double-positive cells express the two receptors in overlapping membrane domains. Three subpopulations of TF-1 cells were categorized based on their levels of surface CXCR4 expression, defined as non-, low-, and high-expressing. Flow cytometry indicated that treatment with DAMGO resulted in a shift in the relative proportion of CXCR4+ cells to the low-expressing phenotype. This result correlated with a >3-fold reduction in replication of the X4 HIV-1 strain IIIB, indicating a role for the CXCR4 high-expression subpopulation in sustaining infection within this progenitor cell line.
  
  
  CONCLUSIONS
  These experiments provide insight into the impact of μ-opioid exposure with respect to inhibition of viral replication in this human TF-1 bone marrow progenitor cell line model.
authors.forename: Marianne
authors.initials: M
authors.lastname: Strazza
authors.forename: Anupam
authors.initials: A
authors.lastname: Banerjee
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Alexaki
authors.forename: Shendra R
authors.initials: SR
authors.lastname: Passic
authors.forename: Olimpia
authors.initials: O
authors.lastname: Meucci
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pirrone
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N, 15th Street, MS# 1013A, Philadelphia, PA 19102, USA. mnonnema@drexelmed.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Nonnemacher
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D006801:Humans; D021381:Protein Transport / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-