title: Morphine enhances HIV infection of human blood mononuclear phagocytes through modulation of beta-chemokines and CCR5 receptor.
abstract: BACKGROUND
  Injection drug use remains a significant risk for acquiring HIV infection. The mechanisms by which morphine enhances HIV infection of human immune cells are largely unknown.
  
  
  OBJECTIVE
  In this study, we sought to determine the possible mechanisms by which morphine upregulates HIV infection of human blood monocyte-derived macrophages (MDM).
  
  
  METHODS
  In this study, MDM were infected with the R5, X4, and R5X4 HIV strains. HIV replication was determined by performing reverse transcriptase activity assays. HIV receptors were determined by performing reverse transcriptase polymerase chain reactions and flow cytometry assays. beta-chemokines were analyzed by performing enzyme-linked immunosorbent assays. In addition, HIV R5 strain and murine leukemia virus envelope-pseudotyped HIV infection was performed to determine whether morphine affects HIV infection of macrophages at entry level.
  
  
  RESULTS
  Morphine significantly enhanced HIV R5 strain infection of MDM but had little effect on X4 strain infection. The macrophage-tropic R5 strain envelope-pseudotyped HIV infection was markedly increased by morphine, whereas murine leukemia virus envelope-pseudotyped HIV infection was not significantly affected. Furthermore, morphine significantly upregulated CCR5 receptor expression and inhibited the endogenous production of beta-chemokines in MDM. The opioid receptor antagonist naltrexone blocked the effects of morphine on the production of beta-chemokines.
  
  
  CONCLUSIONS
  Opiates enhance HIV R5 strain infection of macrophages through the downregulation of beta-chemokine production and upregulation of CCR5 receptor expression and may have an important role in HIV immunopathogenesis.
authors.affiliation: Division of Immunologic and Infectious Diseases, Joseph Stokes Jr. Research Institute of The Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Guo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Sha
authors.initials: S
authors.lastname: Tian
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D019742:Chemokines, CC / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D013045:Species Specificity; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019742:Chemokines, CC; D004279:DNA, Viral; D009292:Narcotic Antagonists; D009294:Narcotics; D019713:Receptors, CCR5; D009271:Naltrexone; D009020:Morphine