Chronic ethanol effects on cellular immune responses to hepatitis B virus envelope protein: An immunologic mechanism for induction of persistent viral infection in alcoholics
✍ Scribed by M Geissler; A Gesien; J R Wands
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 850 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Hepatitis B virus (HBV) is the prototypic member of the Hepatitis B virus (HBV) is common in alcoholics and
hepadnavirus family, a group of small, enveloped DNA vimay result in chronic infection. Persistence of HBV infecruses. Members of this family include the woodchuck, tion could be partially caused by the effects of ethanol ground squirrel, heron, and duck hepatitis B viruses. Each on the cellular and humoral immune response to viral viral agent causes acute and chronic infection of the liver in structural proteins. The DNA-based immunization aptheir respective hosts. 1 Chronic HBV infection is a significant proach was used to experimentally assess the effects of cause of liver disease in the world today and leads to chronic chronic ethanol feeding on immune responses directed active hepatitis, liver cirrhosis, and hepatocellular carcinoma against the middle envelope protein (MHBs) of HBV.
(HCC). Indeed, there is an approximate 100-fold increased Mice were fed an ethanol or isocaloric, pair-fed control risk of developing HCC in chronic HBV carriers as compared liquid diet for 8 weeks, followed by immunization with to noninfected individuals. a plasmid construct containing the pre-S2/S gene that Cellular and humoral immune responses to different HBV encodes for MHBs. Chronic ethanol consumption marginproteins are believed to play an essential role in the eliminaally reduced the levels of the antibody to hepatitis B tion of virus by the host. It is well-established that the husurface proteins (anti-HBs) generated by the DNA-based moral immune response to HBV envelope proteins leads to immunization approach. Initially, cytotoxic lymphocyte protection against reinfection. In contrast, a broad-based cel-(CTL) activity was higher in ethanol-fed mice but prolular immune response may be one of the most important gressively declined following the second and third immufactors that contributes to the elimination of virus from innizations as compared with control mice. In addition, fected hepatocytes. 2 In addition, the cellular immune re-CTL and CD4 / T helper (TH) cells responded poorly to sponse to viral structural proteins may also play an important increasing concentrations of envelope protein and peprole in the pathogenesis of liver cell injury and the subsetides in vitro with respect to generation of CTL activity quent development of chronic liver disease and cirrhosis. An and proliferative responses. Finally, proliferating CD4 / attractive hypothesis for the development of persistent viral T cells derived from ethanol-fed animals had substantial infection is that HBV-specific cellular immune responses are changes in the levels of cytokines secreted into the culunable to clear virus from the liver due to quantitative or ture supernatants as compared with control mice. These qualitative changes within T-cell effector populations. 2 studies show that chronic ethanol consumption substan-Previous studies have presented evidence that alcoholics tially alters the cellular immune responses to a human with liver disease have enhanced exposure to HBV as deterviral structural protein, and that these effects may conmined by the presence of antibodies to the envelope (antitribute to the persistence of viral infection. (HEPATOLOGY HBs) and core (anti-HBc) proteins in blood. The higher fre-1997; 26:764-770.)
quency of these antibodies in alcoholics with liver disease than in nonalcoholic individuals suggests that exposure and possible subsequent acquisition of persistent HBV infection Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; anti-HBs, antibody to hepatitis B surface protein; HBsAg, hepatitis B surface antigen; MHBs, may be a consequence of alcohol abuse. [3][4][5] With the developmiddle envelope protein; CTL, cytotoxic lymphocyte; TH, T helper; mAb, monoclonal ment of molecular biologic techniques to detect HBV DNA antibody; RIA, radioimmunoassay.