Morphine enhances hepatitis C virus (HCV) replicon expression.

Li Y, Zhang T, Douglas SD, Lai JP, Xiao WD, Pleasure DE, Ho WZ.

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.

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.

PMID: 12937158 [PubMed - indexed for MEDLINE]