Peroxisome proliferator-activated receptor gamma Coactivator 1alpha and small heterodimer partner differentially regulate nuclear receptor-dependent hepatitis B virus biosynthesis
| Autor: | Caitlin R. Ondracek, Christel Rushing, Vanessa C. Reese, Alan McLachlan, Claudia E. Oropeza |
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| Rok vydání: | 2009 |
| Předmět: |
Hepatitis B virus
Transcription Genetic Immunology Peroxisome proliferator-activated receptor Receptors Cytoplasmic and Nuclear Biology Virus Replication Microbiology Cell Line Virology Humans Heat-Shock Proteins PELP-1 chemistry.chemical_classification Retinoid X receptor alpha Liver receptor homolog-1 Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Cell biology Virus-Cell Interactions Nuclear receptor coactivator 1 chemistry Nuclear receptor Insect Science Nuclear receptor coactivator 3 Host-Pathogen Interactions Cancer research Small heterodimer partner RNA Viral Transcription Factors |
| Zdroj: | Journal of virology. 83(23) |
| ISSN: | 1098-5514 |
| Popis: | Hepatitis B virus (HBV) biosynthesis involves the transcription of the 3.5-kb viral pregenomic RNA, followed by its reverse transcription into viral DNA. Consequently, the modulation of viral transcription influences the level of virus production. Nuclear receptors are the only transcription factors known to support viral pregenomic RNA transcription and replication. The coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and corepressor small heterodimer partner (SHP) have central roles in regulating energy homeostasis in the liver by modulating the transcriptional activities of nuclear receptors. Therefore, the effect of PGC1α and SHP on HBV transcription and replication mediated by nuclear receptors was examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells. This analysis indicated that viral replication mediated by hepatocyte nuclear factor 4α, retinoid X receptor α (RXRα) plus peroxisome proliferator-activated receptor α (PPARα), and estrogen-related receptor (ERR) displayed differential sensitivity to PGC1α activation and SHP inhibition. The effects of PGC1α and SHP on viral biosynthesis in the human hepatoma cell line Huh7 were similar to those observed in the nonhepatoma cells expressing ERRα and ERRγ. This suggests that these nuclear receptors, potentially in combination with RXRα plus PPARα, may have a major role in governing HBV transcription and replication in this cell line. Additionally, this functional approach may help to distinguish the transcription factors in various liver cells governing viral biosynthesis under a variety of physiologically relevant conditions. |
| Databáze: | OpenAIRE |
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