Hepatitis B virus X region messenger RNA (HBV X mRNA) (HBV X mRNA)

The Hepatitis B virus (HBV) X region messenger RNA (mRNA) is a critical component of the HBV life cycle, encoding the HBx protein, which is essential for viral replication and pathogenesis (Decorsière et al., Nature 2016). HBx acts as a multifunctional transactivator that modulates host cell signaling pathways and degrades the Smc5/6 complex, a host restriction factor that otherwise silences the viral cccDNA (Murphy et al., Gastroenterology 2016). Because the HBV genome utilizes overlapping reading frames and a common 3' polyadenylation signal, the X region sequence is present in all major viral transcripts, including the pregenomic RNA (pgRNA) and subgenomic RNAs (Wooddell et al., Sci Transl Med 2013). This makes the X region an ideal target for RNA-targeted therapies like RNA interference (RNAi) and antisense oligonucleotides (ASOs), as a single trigger can lead to the degradation of all viral mRNA species. Clinical candidates such as Bepirovirsen and JNJ-3989 target this region to reduce the production of viral proteins like HBsAg, aiming to restore the host immune response and achieve a functional cure for chronic hepatitis B (Yuen et al., NEJM 2022; Yuen et al., Lancet Gastroenterol Hepatol 2021). By lowering the burden of viral antigens, these therapies seek to overcome the immune exhaustion characteristic of chronic infection. The degradation of the X region mRNA specifically prevents the synthesis of the HBx protein, thereby hindering the maintenance of cccDNA activity. This target is central to the current paradigm of "functional cure" research in the field of hepatology.

Other names

HBx mRNAHepatitis B virus X gene transcriptHBV X transcriptHBV X-gene mRNA

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