Distinct Regulation of Hepatitis B Virus Biosynthesis by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α and Small Heterodimer Partner in Human Hepatoma Cell Lines.

The human hepatoma cell lines HepG2 and Huh7 have been used extensively to study hepatitis B virus (HBV) transcription and replication. Both cell lines support transcription of the 3.5-kb viral pregenomic RNA and subsequent viral DNA synthesis by reverse transcription. The effects of the coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and corepressor small heterodimer partner (SHP) on HBV transcription and replication mediated by nuclear receptors were examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells in an attempt to determine the relative contribution of the various nuclear receptors to viral biosynthesis in the hepatoma cells. PGC1α and SHP modulated viral biosynthesis differently in the human hepatoma cell lines HepG2 and Huh7, indicating distinct modes of transcriptional regulation. Consistent with this suggestion, it appears that retinoid X receptor α/farnesoid X receptor α and liver receptor homolog 1 or estrogen-related receptor β (ERRβ) may contribute to the majority of the viral replication observed in HepG2 cells, whereas ERRα and ERRγ are probably responsible for the majority of viral biosynthesis in Huh7 cells. Therefore, this approach indicates that the transcriptional regulation of HBV biosynthesis in HepG2 and Huh7 cells is primarily controlled by different transcription factors. [ABSTRACT FROM AUTHOR]