title: Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: an alternative mechanism of HBx-related pathogenesis.
abstract: The role of the hepatitis B virus X protein (HBx) in the pathogenesis of hepatitis B virus (HBV) infection remains unclear. HBx exhibits pleiotropic biological effects, whose in vivo relevance is a matter for debate. In the present report, we have used a combination of HBx-expressing transgenic mice and liver cell transplantation to investigate the in vivo impact of HBx expression on liver cell proliferation and viability in a regenerative context. We show that moderate HBx expression inhibits liver regeneration after partial hepatectomy in HBx-expressing transgenic mice. We also demonstrate that the transplantation of HBx-expressing liver cells, isolated from HBx transgenic mice, is sufficient to inhibit overall recipient liver regeneration after partial hepatectomy. Moreover, the injection of serum samples drawn from HBx-expressing transgenic mice mimicked the inhibitory effect of HBx on liver regeneration. Finally, the incubation of primary rat hepatocytes with the supernatant of HBx-expressing liver cells inhibits cellular DNA synthesis. Taken together, our results demonstrate a paracrine inhibitory effect of HBx on liver cell proliferation and lead us to propose HBV as one of the few viruses implicated in human cancer which act, at least in part, through paracrine biological pathways.
authors: Institut Pasteur-Institut National de la Santé et de la Recherche Médicale Unit 370, Necker Institute, 75015 Paris, France.
authors: J Guilherme
authors: JG
authors: Tralhao
authors: Jean
authors: J
authors: Roudier
authors: Serban
authors: S
authors: Morosan
authors: Carlo
authors: C
authors: Giannini
authors: Hong
authors: H
authors: Tu
authors: Cyril
authors: C
authors: Goulenok
authors: Françoise
authors: F
authors: Carnot
authors: Flora
authors: F
authors: Zavala
authors: Virginie
authors: V
authors: Joulin
authors: Dina
authors: D
authors: Kremsdorf
authors: Christian
authors: C
authors: Bréchot
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D019899:Paracrine Communication; D051381:Rats; D017208:Rats, Wistar; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein