Ethanol inhibition: the humoral and cellular immune response to hepatitis C virus NS5 protein after genetic immunization.
BACKGROUND
The combination of chronic hepatitis C virus (HCV) and ethanol may increase viral replication, impair cellular immunity, and result in severe and progressive liver disease. Because HCV nonstructural proteins play a major role in viral elimination, we examined the cellular and humoral immune responses after genetic immunization against NS5 in a chronic ethanol mouse model.


METHODS
Mice were fed an ethanol or isocaloric pair-fed control liquid diet and were immunized with HCV NS5-expression plasmid.


RESULTS
The humoral and cellular arms of the immune system were significantly impaired in ethanol-fed mice. Abstinence partially reversed the inhibitory effects on antibody levels and the CD4+ proliferative immune response but did not restore the CD8+ cytotoxic T-cell response to this HCV nonstructural protein. Furthermore, we determined whether murine interleukin-2 coadministration with the NS5 expression plasmid would reverse the inhibitory effects of chronic ethanol consumption; again, partial restoration was observed for B-cell and CD4+ T-cell activity, but not for cytotoxic T cells.


CONCLUSIONS
These results suggest that the high rate of chronic HCV infection in alcoholics may be due to ethanol's effects on antiviral immune responses.
Encke
J
J
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, USA.
Wands
J R
JR
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D018937:Hepatitis C Antibodies / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000276:immunology* / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
D002492:Central Nervous System Depressants; D016207:Cytokines; D000431:Ethanol; D018937:Hepatitis C Antibodies; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase