Background: Opioids exert a profound influence on immunomodulation and enhance HIV infection and replication.\r\nHowever, the mechanism(s) of their action remains to be determined. We thus investigated the impact of morphine on the\r\nintracellular innate antiviral immunity.\r\nMethodology/Principal Findings: Seven-day-cultured macrophages were infected with equal amounts of cell-free HIV Bal\r\nor SIV DeltaB670 for 2 h at 37uC after 24 h of treatment with or without morphine. Effect of morphine on HIV/SIV infection\r\nand replication was evaluated by HIV/SIV RT activity assay and indirect immunofluorescence for HIV p24 or SIV p28 antigen.\r\nThe mRNA expression of cellular factors suppressed or induced by morphine treatment was analyzed by the real-time RTPCR.\r\nWe demonstrated that morphine treatment of human blood monocyte-derived macrophages significantly inhibited\r\nthe expression of interferons (IFN-a, IFN-b and IFN-l) and IFN-inducible genes (APOBEC3C/3F/3G and 3H). The further\r\nexperiments showed that morphine suppressed the expression of several key elements (RIG-I and IRF-7) in IFN signaling\r\npathway. In addition, morphine treatment induced the expression of suppressor of cytokine signaling protein-1, 2, 3 (SOCS-\r\n1, 2, 3) and protein inhibitors of activated STAT-1, 3, X, Y (PIAS-1, 3, X, Y), the key negative regulators of IFN signaling\r\npathway.\r\nConclusions: These findings indicate that morphine impairs intracellular innate antiviral mechanism(s) in macrophages,\r\ncontributing to cell susceptibility to AIDS virus infection.
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