Published online Jan 14, 2014. doi: 10.3748/wjg.v20.i2.425
Revised: September 17, 2013
Accepted: October 19, 2013
Published online: January 14, 2014
The core promoter (CP) of the viral genome plays an important role for hepatitis B virus (HBV) replication as it directs initiation of transcription for the synthesis of both the precore and pregenomic (pg) RNAs. The CP consists of the upper regulatory region and the basal core promoter (BCP). The CP overlaps with the 3’-end of the X open reading frames and the 5’-end of the precore region, and contains cis-acting elements that can independently direct transcription of the precore mRNA and pgRNA. Its transcription regulation is under strict control of viral and cellular factors. Even though this regulatory region exhibits high sequence conservation, when variations appear, they may contribute to the persistence of HBV within the host, leading to chronic infection and cirrhosis, and eventually, hepatocellular carcinoma. Among CP sequence variations, those occurring at BCP may dysregulate viral gene expression with emphasis in the hepatitis B e antigen, and contribute to disease progression. In this review these molecular aspects and pathologic topics of core promoter are deeply evaluated.
Core tip: This review summarized the progress in our understanding of the core promoter of hepatitis B virus. This critical genomic region is involved in regulating hepatitis B virus (HBV) gene expression and viral replication, involving both host and virus-derived factors on its regulation. Such pivotal functions appear modified when genomic variations are detected and clinical implications are characterized. This review emphasizes several aspects of the HBV core promoter molecular biology and highlights its role on HBV life cycle. Finally, the most frequent genomic variations with their consequent clinical correlations are described.