Publications & Reports

The hepatitis B e antigen suppresses IL-1beta-mediated NF-kappaB activation in hepatocytes.

Wilson R, Warner N, Ryan K, Selleck L, Colledge D, Rodgers S, Li K, Revill P, Locarnini S
Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia.


Previous clinical studies have demonstrated an association between the hepatitis B e antigen and Toll-like receptor (TLR) expression and signalling. Therefore, the aim of this study was to develop an in vitro assay to measure the effect of hepatitis B virus proteins, including the precore protein, on signalling mediated by members of the Toll-like/interleukin 1 (TIR) superfamily, by measuring NF-kappaB promoter activity. The basal level of NF-kappaB reporter activity was measured in three hepatocyte cell lines (Huh7, HepG2 and PH5CH8) and one kidney cell line (HEK293) using a luciferase assay. All cell lines were virtually refractory to stimulation with lipopolysaccharide; however, PH5CH8 cells had a robust activation of NF-kappaB in response to IL-1beta stimulation, with approximately 40-fold higher activation than the unstimulated control, a higher degree of activation than that observed in either Huh7 and HepG2, or HEK293 and HEK293-TLR2 cells. In PH5CH8 cells transfected with pCI expression constructs and stimulated with IL-1beta, we showed that the precursor form of the precore protein, p25, inhibits NF-kappaB activation by up to 30% and the cytosolic form, p22, inhibits NF-kappaB activation by 70%. The core protein, p21, which shares significant homology with the precore protein except for a 10-amino acid extension at the N-terminus, had no effect on NF-kappaB activation. We hypothesize that the inhibition of IL-1beta-mediated NF-kappaB activation by the precore protein may be a mechanism that allows the virus to persist, suggesting a role for the pool of precore protein that remains intracellular.


  • Journal: Journal of Viral Hepatitis
  • Published: 01/10/2011
  • Volume: 18
  • Issue: 10
  • Pagination: e499-e507

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