Methamphetamine enhances Hepatitis C virus replication in human hepatocytes.
Very little is known about the interactions between hepatitis C virus (HCV) and methamphetamine, which is a highly abused psychostimulant and a known risk factor for human immunodeficiency virus (HIV)/HCV infection. This study examined whether methamphetamine has the ability to inhibit innate immunity in the host cells, facilitating HCV replication in human hepatocytes. Methamphetamine inhibited intracellular interferon alpha expression in human hepatocytes, which was associated with the increase in HCV replication. In addition, methamphetamine also compromised the anti-HCV effect of recombinant interferon alpha. Further investigation of mechanism(s) responsible for the methamphetamine action revealed that methamphetamine was able to inhibit the expression of the signal transducer and activator of transcription 1, a key modulator in interferon-mediated immune and biological responses. Methamphetamine also down-regulated the expression of interferon regulatory factor-5, a crucial transcriptional factor that activates the interferon pathway. These in vitro findings that methamphetamine compromises interferon alpha-mediated innate immunity against HCV infection indicate that methamphetamine may have a cofactor role in the immunopathogenesis of HCV disease.
Ye
L
L
Division of Allergy & Immunology, Joseph Stokes, Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Peng
J S
JS
Wang
X
X
Wang
Y J
YJ
Luo
G X
GX
Ho
W Z
WZ
D015153:Blotting, Western; D002460:Cell Line; D015536:Down-Regulation; D016174:Hepacivirus / Q000254:growth & development*; D022781:Hepatocytes / Q000187:drug effects* / Q000821:virology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D050835:Interferon Regulatory Factors / Q000037:antagonists & inhibitors; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D008694:Methamphetamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects*
C431713:IRF5 protein, human; D007166:Immunosuppressive Agents; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D008694:Methamphetamine