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Hepatitis B virus (HBV) X protein-mediated regulation of hepatocyte metabolic pathways affects viral replication
Journal article   Open access   Peer reviewed

Hepatitis B virus (HBV) X protein-mediated regulation of hepatocyte metabolic pathways affects viral replication

Sumedha Bagga, Siddhartha Rawat, Marcia Ajenjo and Michael J Bouchard
Virology (New York, N.Y.), v 498, pp 9-22
Nov 2016
PMID: 27529294
url
https://doi.org/10.1016/j.virol.2016.08.006View
Published, Version of Record (VoR)Open Access (Publisher-Specific) Open

Abstract

Adenosine Triphosphate - metabolism AMP-Activated Protein Kinases - metabolism Animals Cells, Cultured Hepatitis B - metabolism Hepatitis B - virology Hepatitis B virus - physiology Hepatocytes - metabolism Hepatocytes - virology Mechanistic Target of Rapamycin Complex 1 Metabolic Networks and Pathways Multiprotein Complexes - metabolism Protein Binding Rats Signal Transduction TOR Serine-Threonine Kinases - metabolism Trans-Activators - metabolism Virus Replication
Chronic HBV infection is a risk factor for hepatocellular carcinoma (HCC). The HBV HBx protein stimulates HBV replication and likely influences the development of HBV-associated HCC. Whether HBx affects regulators of metabolism in normal hepatocytes has not been addressed. We used an ex vivo, cultured primary rat hepatocyte system to assess the interplay between HBV replication and mechanistic target of rapamycin complex 1 (mTORC1) signaling. HBx activated mTORC1 signaling; however, inhibition of mTORC1 enhanced HBV replication. HBx also decreased ATP levels and activated the energy-sensing factor AMP-activated protein kinase (AMPK). Inhibition of AMPK decreased HBV replication. Inhibition of AMPK activates mTORC1, and we showed that activated mTORC1 is one factor that reduces HBV replication when AMPK is inhibited. HBx activation of both AMPK and mTORC1 suggests that these activities could provide a balancing mechanism to facilitate persistent HBV replication. HBx activation of mTORC1 and AMPK could also influence HCC development.

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Collaboration types
International collaboration
Web of Science research areas
Virology
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