Novel HBx-interacting host cellular factors regulate dynamic nuclear and cytoplasmic localization of Hepatitis B virus X protein (HBx).

The hepatitis B virus (HBV) X protein (HBx) is a key player in viral transcription, replication, and HBV-associated hepatocarcinogenesis. Several novel HBx-interacting host cellular factors: DDX1, DDX3, MOV10 RNA helicases, INI1/hSNF5 chromatin-remodeling factor, Rad18 DNA repair enzyme, and CPSF6 cleavage factor were identified. DDX1, DDX3, and MOV10 colocalized with HBx in cytoplasmic foci or aggregates. In contrast, INI1/hSNF5 and CPSF6 relocalized with HBx in nuclear speckles, interchromatin granule clusters (IGCs), and/or PML-nuclear bodies. Rad18 sequestered HBx in the nucleoli. Importantly, DDX3, MOV10, and INI1/hSNF5 restricted HBV replication, whereas CPSF6 facilitated HBV replication. Furthermore, DDX1 enhanced HBx-mediated NF-κB transcription, whereas MOV10 and Rad18 inhibited it. Altogether, HBx-interacting host factors determine dynamic nuclear and cytoplasmic localization of HBx and regulate HBV replication and HBx-mediated transcription.