title: Role of peroxisome proliferator-activated receptor gamma coactivator 1alpha in AKT/PKB-mediated inhibition of hepatitis B virus biosynthesis.
abstract: Hepatitis B virus (HBV) transcription and replication are essentially restricted to hepatocytes because liver-enriched transcription factors govern viral RNA synthesis. The level of transcription from the HBV promoters depends on both the transcription factors binding to these regulatory sequence elements and their ability to recruit coactivators capable of mediating assembly of the transcription preinitiation complex containing RNA polymerase II. Nuclear receptors are a primary determinant of HBV pregenomic RNA synthesis and, hence, viral replication. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) enhances the activity of nuclear receptors and, consequently, HBV biosynthesis. PGC1α is also an important target of signal transduction pathways involved in hepatic glucose and lipid homeostasis, suggesting that this coactivator may have an important role in modulating HBV biosynthesis under various physiological conditions. Consistent with this suggestion, v-akt murine thymoma viral oncogene homolog/protein kinase B (AKT/PKB) is shown to modulate PGC1α activity and, hence, HBV transcription and replication in a cell line-specific manner. In addition, AKT can modulate HBV replication in some but not all cell lines at a posttranscriptional step in the viral life cycle. These observations demonstrate that growth and nutritional signals have the capacity to influence viral production, but the magnitude of these effects will depend on the precise cellular context in which they occur.
authors: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 909 South Wolcott Avenue, Chicago, IL 60612, USA.
authors: Caitlin R
authors: CR
authors: Ondracek
authors: Alan
authors: A
authors: McLachlan
mesh_terms: D002460:Cell Line; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt