title: Hepatocyte metabolic signalling pathways and regulation of hepatitis B virus expression.
abstract: Hepatitis B virus (HBV) is a small DNA virus responsible for significant morbidity and mortality worldwide. The liver, which is the main target organ for HBV infection, provides the virus with the machinery necessary for persistent infection and propagation, a process that might ultimately lead to severe liver pathologies such as chronic hepatitis, cirrhosis and liver cancer. HBV gene expression is regulated mainly at the transcriptional level by recruitment of a whole set of cellular transcription factors (TFs) and co-activators to support transcription. Over the years, many of these TFs were identified and interestingly enough most are associated with the body's nutritional state. These include the hepatocyte nuclear factors, forkhead Box O1, Farnesoid X receptor, cyclic-AMP response element-binding (CREB), CCAAT/enhancer-binding protein (C/EBP) and glucocorticoid receptor TFs and the transcription coactivator PPARγ coactivator-1α. Consequently, HBV gene expression is linked to hepatic metabolic processes such as glucose and fat production and utilization as well as bile acids' production and secretion. Furthermore, recent evidence indicates that HBV actively interferes with some of these hepatic metabolic processes by manipulating key TFs, such as CREB and C/EBP, to meet its requirements. The discovery of the mechanisms by which HBV is controlled by the hepatic metabolic milieu may broaden our understanding of the unique regulation of HBV expression and may also explain the mechanisms by which HBV induces liver pathologies. The emerging principle of the intimate link between HBV and liver metabolism can be further exploited for host-targeted therapeutic strategies.
authors.affiliation: The Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Iddo
authors.initials: I
authors.lastname: Bar-Yishay
authors.forename: Yosef
authors.initials: Y
authors.lastname: Shaul
authors.forename: Amir
authors.initials: A
authors.lastname: Shlomai
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000378:metabolism* / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D015415:Biomarkers