Hepatitis B virus X region transcripts (HBV X mRNA)

Hepatitis B virus (HBV) X region transcripts are the messenger RNA sequences produced from the X open reading frame of the HBV genome, which encode the multifunctional HBx protein. The HBx protein is essential for the initiation and maintenance of viral replication, as it facilitates transcription from the covalently closed circular DNA (cccDNA) template by degrading the Smc5/6 restriction factor (Decorsière et al., Nature, 2016; https://www.nature.com/articles/nature17170). Beyond its role in the viral lifecycle, HBx is a well-characterized oncoprotein that contributes to the development of hepatocellular carcinoma (HCC) by interfering with host DNA repair mechanisms and modulating signal transduction pathways (Slagle & Bouchard, Frontiers in Bioscience, 2009; https://pubmed.ncbi.nlm.nih.gov/19273096/). Because the HBV genome uses overlapping reading frames, the X region is present in all major viral transcripts, making it a highly strategic target for RNA-targeted therapies. Current therapeutic approaches, including small interfering RNAs (siRNAs) like JNJ-3989 and Vir-2218, or antisense oligonucleotides (ASOs) like Bepirovirsen, are designed to bind and degrade these transcripts (Gane et al., Lancet Infectious Diseases, 2019; https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30059-4/fulltext). This degradation reduces the production of HBx and other viral antigens, aiming to restore the host immune response and achieve a functional cure for chronic hepatitis B (Yuen et al., Lancet Gastroenterology & Hepatology, 2020; https://www.thelancet.com/journals/langas/article/PIIS2468-1253(19)30402-6/fulltext).

Other names

HBx mRNAHepatitis B virus X gene transcriptsHBV X-ORF mRNAHBV X-gene messenger RNA

RNA interference (RNAi) or antisense-mediated degradation of viral mRNA to prevent the translation of the HBx protein and other overlapping viral proteins.