epidermal-growth-factor and Hepatitis--Viral--Animal

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.. 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.. EGF induced cell proliferation is associated with a slight increase in CCC DNA synthesis and a decrease in viral transcription. Conversely, TGFbeta blocked cell cycle progression, diminished CCC DNA synthesis but increased viral transcription.. 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.

Topics: Animals; Cell Division; Chick Embryo; Chronic Disease; DNA, Viral; Ducks; Epidermal Growth Factor; Gene Expression Regulation, Viral; Hepadnaviridae Infections; Hepatitis B Virus, Duck; Hepatitis, Viral, Animal; Hepatocytes; Liver Regeneration; RNA, Viral; Transcription, Genetic; Transforming Growth Factor beta; Virus Replication

Hepatic regeneration in partially hepatectomized, eviscerated rats, and survival in mice infected with lethal doses of murine hepatitis virus, are both strikingly promoted by combined administration of insulin and glucagon. These two hormones, although potent promotors, fail as initiators of hepatocyte proliferation in animals with intact liver, which suggests a requirement for additional factors, probably derived from non-portal-splanchnic organs. We now find that continous intraperitoneal infusion of epidermal growth factor (EGF) initiates DNA synthesis, as determined by incorporation of [3H] thymidine, in livers of adult rats in vivo. The rise in DNA labelling, which is small with EGF alone, is augmented by addition to the infusion of either glucagon or insulin. This is in agreement with reports on adult hepatocytes in culture. Whether EGF has a physiological role in regulating liver growth under normal conditions in vivo remains to be determined.

Topics: Age Factors; Animals; Cell Division; DNA Replication; Epidermal Growth Factor; Glucagon; Hepatectomy; Hepatitis, Viral, Animal; In Vitro Techniques; Insulin; Liver Regeneration; Male; Mice; Peptides; Rats