A diagrammatic representation of the HBV genome. The inner circle represents the virion genomic DNA that is packaged within viral particles in the cytoplasm of infected cells, and the dashes indicate the region of the genome which is incompletely synthesized. The thick arrows represent open reading frames corresponding to core, envelope (surface antigen), polymerase (pol), and HBx proteins. The thin lines represent HBV RNAs.

Targets of HBx activity. Arrows indicate pathways and targets of HBx activity. Filled arrows represent more-certain primary targets or activities of HBx, whereas dotted arrows are likely secondary targets or have not been widely validated. HBx likely binds directly to the transcription factor CREB and possibly to transcription factors TFIIB, TFIIH, and the RNA polymerase II-associated protein RPB5, but the latter might interact with HBx via secondary interactions with CREB. HBx-CREB transcription complexes have been shown to stimulate transcription. HBx is thought to act on the mitochondria, causing calcium release, in turn activating the Pyk2/FAK and Src kinase families, leading to stimulation of a variety of cytoplasmic signal transduction pathways. HBx activation of signaling pathways can stimulate phosphorylation and activation of transcription factors, as indicated, as well as viral replication. Interaction of HBx with the UV-DDB proteins (1 and/or 2) is implicated in stimulation of viral replication. HBx interaction with the proteasome is also reported to stimulate HBV replication.