Chronic ethanol effects on cellular immune responses to hepatitis B virus envelope protein: an immunologic mechanism for induction of persistent viral infection in alcoholics.

Hepatitis B virus (HBV) is common in alcoholics and may result in chronic 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 on immune responses directed against the middle envelope protein (MHBs) of HBV. Mice were fed an ethanol or isocaloric, pair-fed control liquid diet for 8 weeks, followed by immunization with a plasmid construct containing the pre-S2/S gene that encodes for MHBs. Chronic ethanol consumption 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 and CD4+ T helper (TH) cells responded poorly to increasing concentrations of envelope protein and peptides in vitro with respect to generation of CTL activity and proliferative responses. Finally, proliferating CD4+ T cells derived from ethanol-fed animals had substantial changes 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 human viral structural protein, and that these effects may contribute to the persistence of viral infection.