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.
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, USA.
J
J
Encke
J R
JR
Wands
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