CHRONIC ETHANOL EFFECTS ON CELLULAR IMMUNE-RESPONSES TO HEPATITIS-B VIRUS ENVELOPE PROTEIN - AN IMMUNOLOGICAL MECHANISM FOR INDUCTION OF PERSISTENT VIRAL-INFECTION IN ALCOHOLICS

Hepatitis B virus (HBV) is common in alcoholics and may result in chro nic infection. Persistence of HBV infection could be partially caused by the effects of ethanol on the cellular and humoral immune response to viral structural proteins. The DNA-based immunization approach was used to experimentally assess the effects of chronic ethanol feeding o n immune responses directed against the middle envelope protein (MHBs) of HBV. Mice were fed an ethanol or isocaloric, pair-fed control liqu id diet for 8 weeks, followed by immunization with a plasmid construct containing the pre-S2/S gene that encodes for MHBs. Chronic ethanol c onsumption marginally reduced the levels of the antibody to hepatitis B surface proteins (anti-HBs) generated by the DNA-based immunization approach. Initially, cytotoxic lymphocyte (CTL) activity was higher in ethanol-fed mice but progressively declined following the second and third immunizations as compared with control mice. In addition, CTL an d CD4(+) T helper (TH) cells responded poorly to increasing concentrat ions of envelope protein and peptides in vitro with respect to generat ion of CTL activity and proliferative responses. Finally, proliferatin g CD4(+) T cells derived from ethanol-fed animals had substantial chan ges in the levels of cytokines secreted into the culture supernatants as compared with control mice, These studies show that chronic ethanol consumption substantially alters the cellular immune responses to a h uman viral structural protein, and that these effects may contribute t o the persistence of viral infection.