**2. Organization of HBV cccDNA and its transcriptional control**

Hepatitis B virus (HBV) is a partially double-stranded circular DNA virus [8]. The viral DNA goes into nuclei of infected hepatocytes where it is converted to cccDNA [8]. The cccDNA is a viral minichromosome, which takes the form of "beads-on-a-string" conformation of nucleosomal packaging [9], analogous to DNA packaging by mammalian nucleosome. HBV core protein and X protein along with histone H3 and H4 are components of HBV minichromosome [9–11]. A variety of cellular transcription factors bind HBV cccDNA, which in turn control transcriptional activity of HBV promoters: the preC/pregenomic, S1, S2, and X promoters [12]. The core promoter initiates transcription of preC and pregenomic RNA, the template for the viral genome by reverse transcription. Ubiquitous transcription factors such as specificity protein 1 (SP1), nuclear factor kappa B (NF-κβ), activator protein 1 (AP-1), and liver-enriched transcription factors such as hepatocyte nuclear factor 3 (HNF3), CAAT enhancer-binding protein (C/EBP), and several nuclear receptors such as hepatocyte nuclear factor 4 (HNF4), peroxisome proliferator-activated receptors (PPAR) and retinoid X receptors (RXRα), farnesoid acid receptor (FXR), small heterodimer partner (SHP), and testicular orphan receptor 4 (TR4) can bind core promoter [13, 14].
