Effects of liver growth factors on hepadnavirus replication in chronically infected duck hepatocytes

Background/Aims Duck hepatitis B virus (DHBV) replication is up-regulated by cell cycle during the early infection of primary duck but the effect of cell cycle on DHBV replication in chronically infected hepatocyte is not known. Methods Hepatocytes obtained from DHBV congenitally infected embryos were used. Cell proliferation was controlled by addition of liver growth factors and the impact on viral replication analyzed. Results EGF induced cell proliferation is associated with a slight increase in CCC DNA synthesis and a decrease in viral transcription. Conversely, TGFβ blocked cell cycle progression, diminished CCC DNA synthesis but increased viral transcription. Conclusions Cell proliferation decreases DHBV transcription but this effect seems to be compensated by an opposite effect on the synthesis of CCC DNA resulting in a global moderate effect on viral replication. Our results also indicate that after division of chronically infected hepatocytes both daughter cells are infected, confirming that liver regeneration is not sufficient to induce CCC DNA eradication as suggested by the lack of effect of some long term anti-HBV therapies.