title: Morphine suppresses IFN signaling pathway and enhances AIDS virus infection.
abstract: BACKGROUND
  Opioids exert a profound influence on immunomodulation and enhance HIV infection and replication. However, the mechanism(s) of their action remains to be determined. We thus investigated the impact of morphine on the intracellular innate antiviral immunity.
  
  
  RESULTS
  Seven-day-cultured macrophages were infected with equal amounts of cell-free HIV Bal or SIV Delta(B670) for 2 h at 37°C after 24 h of treatment with or without morphine. Effect of morphine on HIV/SIV infection and replication was evaluated by HIV/SIV RT activity assay and indirect immunofluorescence for HIV p24 or SIV p28 antigen. The mRNA expression of cellular factors suppressed or induced by morphine treatment was analyzed by the real-time RT-PCR. We demonstrated that morphine treatment of human blood monocyte-derived macrophages significantly inhibited the expression of interferons (IFN-α, IFN-β and IFN-λ) and IFN-inducible genes (APOBEC3C/3F/3G and 3H). The further experiments showed that morphine suppressed the expression of several key elements (RIG-I and IRF-7) in IFN signaling pathway. In addition, morphine treatment induced the expression of suppressor of cytokine signaling protein-1, 2, 3 (SOCS-1, 2, 3) and protein inhibitors of activated STAT-1, 3, X, Y (PIAS-1, 3, X, Y), the key negative regulators of IFN signaling pathway.
  
  
  CONCLUSIONS
  These findings indicate that morphine impairs intracellular innate antiviral mechanism(s) in macrophages, contributing to cell susceptibility to AIDS virus infection.
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Jieliang
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Nilija
authors.initials: N
authors.lastname: Fulambarkar
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D002478:Cells, Cultured; D006678:HIV; D015658:HIV Infections / Q000139:chemically induced*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000821:virology; D009020:Morphine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D015302:Simian Immunodeficiency Virus; D014779:Virus Replication / Q000187:drug effects
chemical_list: D009020:Morphine; D007372:Interferons