The genome organisation of HBV; the genes overlap. ORF X, in yellow, encodes HBx.
HBx is a hepatitis Bviral protein.[1][2] It is 154 amino acids long and interferes with transcription, signal transduction, cell cycle progress, protein degradation, apoptosis and chromosomal stability in the host. It forms a heterodimeric complex with its cellular target protein (HBX interacting protein: HBXIP), and this interaction dysregulates centrosome dynamics and mitotic spindle formation.[3] It interacts with DDB1 (Damaged DNA Binding Protein 1) redirecting the ubiquitin ligase activity of the CUL4-DDB1 E3 complexes, which are intimately involved in the intracellular regulation of DNA replication and repair, transcription and signal transduction.[4]
Although Protein X is normally absent in the Avihepadnavirus, a vestigial version has been identified in the duck hepatitis virus genome.[5]
Although it lacks significant sequence identity with any known vertebrate proteins, it seems likely that it evolved from a DNA glycosylase.[6]
Transgenic mice expressing the X protein in liver are more likely than the wild type to develop hepatocellular carcinoma. This is because the X protein promotes cell cycle progression while binding to and inhibiting tumor suppressor protein p53 from performing its role. Experimental observations also suggest that HBx protein increases TERT and telomerase activity, prolonging the lifespan of hepatocytes and contributing to malignant transformation.[7]