Hepatitis B virus X protein (HBx) (HBx)

The Hepatitis B virus X protein (HBx) is a 154-amino acid regulatory protein essential for the replication and pathogenesis of the Hepatitis B virus (HBV). It functions as a pleiotropic transactivator that modulates the expression of viral and host genes by interacting with various transcription factors and signaling pathways, including the autoregulation of its own expression via the HBx promoter [UniProt, P03402]. A key biological role of HBx is the recruitment of the host DDB1-Cul4 E3 ubiquitin ligase complex to degrade the Smc5/6 complex, which otherwise acts as a restriction factor to silence HBV transcription from the cccDNA template [PubMed, 26983541]. HBx is also a critical factor in the development of HBV-related hepatocellular carcinoma (HCC), as it disrupts DNA repair mechanisms, cell cycle control, and apoptosis in infected hepatocytes [PubMed, 27529271]. Due to its central role in the viral life cycle, HBx is a major target for therapeutic intervention. Current drug development strategies include RNA interference (RNAi) and antisense oligonucleotides (ASOs) designed to silence HBx expression, as well as small molecules that aim to block the HBx-DDB1 interaction to restore host-mediated viral silencing [GSK, https://www.gsk.com/en-gb/media/press-releases/positive-data-for-bepirovirsen-from-b-clear-phase-iib-trial-published-in-new-england-journal-of-medicine/].

Other names

HBxAgHepatitis B virus X antigenpXHBV X proteinHepatitis B virus X protein–responsive HBx promoter

Inhibition of viral protein synthesis via RNA interference or antisense oligonucleotides; disruption of HBx-DDB1 interaction to prevent Smc5/6 degradation.