The woodchuck together with the woodchuck hepatitis virus (WHV) is an excellent model to study the pathogenesis of hepadnaviral
infections. Chronic WHV
infection causes severe
liver disease and
hepatocellular carcinoma in woodchucks. The mechanism of viral clearance is not fully understood,
interferons seem to play a major role in down-regulating viral replication prior to elimination of infected hepatocytes. We investigated on the pattern of
cytokine and T-cell-marker expression in livers of woodchucks chronically infected with WHV.
RNase-protection-assay (RPA) was used to determine
mRNA of woodchuck specific genes (
TNF-alpha, IFN-gamma, IL-15, CD3, CD4, CD8). Serial liver biopsies were performed daily or weekly in eight chronic WHV-carrier woodchucks.
Cytokine/T-cell-marker expression differed significantly between the time points up to +/-50% within each woodchuck. The different expression patterns of
cytokines or T-cell-markers did not correlate to the (weak) fluctuations in the
viremia but may explain the observed fluctuations in the WHV/HBV-load in chronically infected individuals. Furthermore, we observed associations between
cytokine and T-cell-marker expression. The marginal fluctuations in
viremia during the
chronic infection may indicate, that, once the chronic hepadnaviral
infection is established,
cytokines/
interferons expressed endogenously (i.e. not vector-borne or injected) play only a minor role.