The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals

摘要

Abstract Virally encoded proteins have evolved to perform multiple functions, and the core protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is the structural component of the viral nucleocapsid, additional novel functions for the nucleus-localized HBc have recently been described. These results extend for HBc, beyond its structural role, a regulatory function in the viral life cycle and potentially a role in pathogenesis. In this article, we review the diverse roles of HBc in HBV replication and pathogenesis, emphasizing how the unique structure of this protein is key to its various functions. We focus in particular on recent advances in understanding the significance of HBc phosphorylations, its interaction with host proteins and the role of HBc in regulating the transcription of host genes. We also briefly allude to the emerging niche for new direct-acting antivirals targeting HBc, known as Core (protein) Allosteric Modulators (CAMs). Highlights ? We review current knowledge of the diverse functions of the hepatitis B core/capsid protein in the viral life cycle. ? The N-terminal HBc 1-140 is sufficient for capsid assembly, while the C-terminal domain is required for replication. ? HBc subcellular localization is a dynamic process, involving active transport, likely influenced by CTD phosphorylations. ? HBc interacts with host factors (protein and lncRNA) and influences viral and host transcription. ? HBc can serve as an effective target for clinical intervention against chronic HBV infection.