Hepatitis B virus X gene region (HBV X region)

The Hepatitis B virus (HBV) X gene region on HBV RNA transcripts is a critical target for modern antiviral strategies, particularly RNA interference (RNAi) and antisense oligonucleotides (ASOs) (Wooddell et al., 2020, Science Translational Medicine). This specific sequence is highly conserved and is present in all major HBV RNA transcripts, including the pregenomic RNA (pgRNA) and subgenomic mRNAs, due to the overlapping nature of the viral genome and the use of a common polyadenylation signal (Gish et al., 2015, Antiviral Research). The X gene encodes the HBx protein, which is essential for the initiation and maintenance of viral transcription from the covalently closed circular DNA (cccDNA) in the host cell nucleus (Mueller et al., 2021, Journal of Hepatology). By targeting this region, therapeutic agents can induce the degradation of all viral RNA species, leading to a comprehensive reduction in the synthesis of all viral proteins, such as HBsAg and HBeAg (Yuen et al., 2021, The Lancet Gastroenterology & Hepatology). This broad suppression of viral antigens is designed to reverse the state of immune exhaustion typically seen in chronic hepatitis B patients, potentially allowing the host's immune system to regain control over the infection (Agarwal et al., 2023, Journal of Hepatology). Clinical candidates like JNJ-3989 and VIR-2218 specifically target this region to achieve significant and sustained reductions in HBsAg levels, moving toward the goal of a functional cure.

Other names

HBx RNAHBV X-ORF transcriptHBV X gene sequenceHepatitis B virus X protein mRNAHBV X-region RNA

RNA interference (RNAi) or antisense-mediated degradation of viral mRNA transcripts to inhibit viral protein synthesis and replication.