Background: The hepatitis B virus (HBV) possesses a circular, partially double-stranded DNA genome of approximately 3.2 kb, organized into four overlapping open reading frames encoding the surface (HBsAg), core (HBcAg), polymerase, and X proteins. Despite its compact genome and extensive gene overlap, HBV maintains exceptional replication fidelity and adaptability. Understanding the molecular organization of its genome, transcriptional regulation, and translational strategies is essential to elucidate how HBV sustains replication and persistence under strong structural constraints. Methods: A detailed genomic and molecular analysis of HBV architecture, transcriptional units, and translational mechanisms was conducted using published data. Emphasis was placed on the functions of pregenomic RNA (pgRNA), preC-RNA, preS1-RNA, and S-RNA, along with structural features of the core and polymerase proteins and HBV-encoded microRNAs. Results: HBV utilizes overlapping open reading frames, shared polyadenylation sites, and leaky scanning to maximize protein diversity from limited coding sequences. The pgRNA serves as both mRNA and replication template, while the polymerase domains (terminal protein, reverse transcriptase, RNase H) coordinate reverse transcription. Viral microRNAs contribute to host–virus regulatory interactions, promoting persistence. Conclusions: HBV exemplifies a highly efficient genetic system that achieves functional complexity within minimal genomic space. Understanding these overlapping mechanisms provides insight into viral replication control and therapeutic target development.

Hepatitis B virus; viral genome; pregenomic RNA; HBV polymerase; core antigen; overlapping open reading frames; reverse transcription; viral microRNA; serotypes; genotypes.