Morphine enhances hepatitis C virus (HCV) replicon expression.
Little information is available regarding whether substance abuse enhances hepatitis C virus (HCV) replication and promotes HCV disease progression. We investigated whether morphine alters HCV mRNA expression in HCV replicon-containing liver cells. Morphine significantly increased HCV mRNA expression, an effect which could be abolished by either of the opioid receptor antagonists, naltrexone or beta-funaltrexamine. Investigation of the mechanism responsible for this enhancement of HCV replicon expression demonstrated that morphine activated NF-kappaB promoter and that caffeic acid phenethyl ester, a specific inhibitor of the activation of NF-kappaB, blocked morphine-activated HCV RNA expression. In addition, morphine compromised the anti-HCV effect of interferon alpha (IFN-alpha). Our in vitro data indicate that morphine may play an important role as a positive regulator of HCV replication in human hepatic cells and may compromise IFN-alpha therapy.
Li
Yuan
Y
Division of Immunologic and Infectious Diseases, Department of Pediatrics, Stokes Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA.
Zhang
Ting
T
Douglas
Steven D
SD
Lai
Jian-Ping
JP
Xiao
Wei-Dong
WD
Pleasure
David E
DE
Ho
Wen-Zhe
WZ
D000998:Antiviral Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D012093:Replicon; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D016898:Interferon-alpha; D016328:NF-kappa B; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine