Hepatitis B virus pregenomic and pre-core RNA (HBV pgRNA/pcRNA)

Hepatitis B virus (HBV) pregenomic RNA (pgRNA) and pre-core RNA (pcRNA) are essential 3.5 kb transcripts transcribed from the covalently closed circular DNA (cccDNA) in the host cell nucleus (Gish et al., 2015). The pgRNA is a multifunctional molecule that serves as the mRNA for the viral core protein and polymerase, and as the template for reverse transcription within the nucleocapsid to generate new DNA genomes (Wang et al., 2016). The pcRNA, which is slightly longer at the 5' end, encodes the pre-core protein that is processed into the hepatitis B e-antigen (HBeAg), a critical factor in modulating the host immune response (Gao et al., 2023). These RNA species are central to the HBV life cycle and are currently targeted by innovative therapies like antisense oligonucleotides (e.g., Bepirovirsen) and siRNAs (e.g., JNJ-3989) to reduce viral load and antigenemia (Yuen et al., 2021). Monitoring serum levels of HBV pgRNA has also emerged as a valuable biomarker for assessing the transcriptional activity of cccDNA, particularly in patients receiving nucleos(t)ide analogue therapy (Mak et al., 2020). By promoting the degradation of these transcripts, these therapeutic strategies aim to achieve a functional cure by significantly reducing the burden of viral antigens and stopping the replication cycle, potentially allowing the host immune system to regain control over the infection.

Other names

HBV pgRNAHBV pcRNA3.5kb RNAPregenomic RNAPrecore RNAHBV 3.5kb transcripts

Degradation of viral RNA transcripts via RNase H-mediated cleavage (ASOs) or RNA interference (siRNAs) to inhibit viral protein synthesis and replication (Yuen et al., 2021; Gane et al., 2020).