Schematic representation of the HBV genome. The genome is approximately 3020 nucleotides long and consists of partially double-stranded DNA. There are four overlapping open reading frames, four promoters, and two enhancer elements to regulate the transcription of viral RNA. The gene S encodes for the HBsAg, and it is a long open reading frame containing three start codons. Thus, the gene is divided into three sections, pre-S1, pre-S2, and S. The core gene consists of the pre-core and core regions, which encode for the HBV e antigen (HBeAg) and core protein, respectively. The polymerase (P) gene overlaps the entire S gene and encodes the viral DNA polymerase. Hepatitis B x antigen (HBxAg) is the smallest gene and is associated with the activation of transcription. The negative-sense strand is complementary to the viral mRNA. Using covalently closed circular DNA (cccDNA) as a template; the viral genes are transcribed by the cellular RNA polymerase II in the nucleus. DR1 and DR2 are 11-base-pair direct repeats that are required for strand-specific DNA synthesis during the HBV replication. Two enhancers (Enh1 and Enh2) exhibit activity in regulating the expression of the complete viral transcripts.