Hepatitis B virus transcription machinery (HBV transcription machinery)

The Hepatitis B virus (HBV) transcription machinery is the multi-component system responsible for synthesizing viral RNA from the covalently closed circular DNA (cccDNA) template within the nucleus of infected hepatocytes (Nassal, 2015). This machinery primarily utilizes the host cell's RNA polymerase II, regulated by viral proteins such as HBx and various host transcription factors and epigenetic modifiers. HBx plays a critical role by facilitating the degradation of the Smc5/6 complex, which otherwise silences cccDNA transcription (Decorsière et al., 2016). In chronic HBV infection, this machinery produces the pregenomic RNA (pgRNA) required for replication and the subgenomic mRNAs that encode viral proteins like HBsAg, which contribute to immune evasion (Fanning et al., 2019). Modern therapeutic strategies target this machinery through RNA interference (RNAi) and antisense oligonucleotides (ASOs) to degrade viral transcripts, or through experimental small molecules designed to epigenetically silence or eliminate the cccDNA template (Gane et al., 2022). By inhibiting the production of viral RNAs and proteins, these therapies aim to restore the host immune response and achieve a functional cure for chronic hepatitis B.

Other names

HBV transcriptional complexHBV RNA production machinerycccDNA transcription machineryHepatitis B virus gene expression machinery

The machinery is targeted by degrading viral mRNA and pregenomic RNA (pgRNA) using RNA interference (RNAi) or antisense oligonucleotides (ASOs), which utilize the RISC complex or RNase H respectively (Wooddell et al., 2020; Gane et al., 2022). Additionally, experimental therapies aim to epigenetically silence the cccDNA template by inhibiting the viral HBx protein or restoring the Smc5/6 restriction complex (Decorsière et al., 2016).