American Journal of Pathology. 2003;163:1167-1175
Morphine Enhances Hepatitis C Virus (HCV) Replicon Expression
Yuan Li*, Ting Zhang*, Steven D. Douglas*, Jian-Ping Lai*, Wei-Dong Xiao*, David E. Pleasure and Wen-Zhe Ho*
From the Divisions of Immunologic and Infectious Diseases,*and Neurology and Neurology Research,Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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 ß-funaltrexamine. Investigation of the mechanism responsible for this enhancement of HCV replicon expression demonstrated that morphine activated NF-B promoter and that caffeic acid phenethyl ester, a specific inhibitor of the activation of NF-B, blocked morphine-activated HCV RNA expression. In addition, morphine compromised the anti-HCV effect of interferon alpha (IFN-). 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- therapy. |
