Several micro RNAs (
miRNAs) have the ability to inhibit HIV replication in target cells. Thus, we investigated the impact of
opioids (
morphine and
heroin), widely abused drugs among people infected with HIV, on the expression of cellular anti-HIV
miRNAs in monocytes. We found that
morphine-treated monocytes expressed lower levels of cellular anti-HIV
miRNAs than untreated cells. In addition,
morphine treatment of monocytes compromised
type I interferon (IFN)-induced anti-HIV
miRNA expression. These findings paralleled the observation that
morphine treatment of monocytes enhanced HIV replication. These
morphine-mediated actions on the anti-HIV
miRNAs and HIV could be antagonized by the
opioid receptor antagonists (
naltrexone or Cys2, Tyr3, Arg5, Pen7-
amide). Furthermore, the in vitro impact of
morphine on
miRNA expression was confirmed by the in vivo observation that
heroin-dependent subjects had significantly lower levels of anti-HIV
miRNAs (
miRNA-28, 125b, 150, and 382) in peripheral blood mononuclear cells than the healthy subjects. These in vitro and in vivo findings indicate that
opioid use impairs intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to
HIV infection.