Hepatitis B virus HBx protein interactions with the ubiquitin proteasome system

Viruses. 2014 Nov 24;6(11):4683-702. doi: 10.3390/v6114683.


The hepatitis B virus (HBV) causes acute and chronic hepatitis, and the latter is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV encodes a 17-kDa regulatory protein, HBx, which is required for virus replication. Although the precise contribution(s) of HBx to virus replication is unknown, many viruses target cellular pathways to create an environment favorable for virus replication. The ubiquitin proteasome system (UPS) is a major conserved cellular pathway that controls several critical processes in the cell by regulating the levels of proteins involved in cell cycle, DNA repair, innate immunity, and other processes. We summarize here the interactions of HBx with components of the UPS, including the CUL4 adaptor DDB1, the cullin regulatory complex CSN, and the 26S proteasome. Understanding how these protein interactions benefit virus replication remains a challenge due to limited models in which to study HBV replication. However, studies from other viral systems that similarly target the UPS provide insight into possible strategies used by HBV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cullin Proteins
  • DNA-Binding Proteins
  • Hepatitis B virus / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Interaction Maps*
  • Trans-Activators / metabolism*
  • Ubiquitin / metabolism*
  • Virus Replication


  • CUL4A protein, human
  • Cullin Proteins
  • DDB1 protein, human
  • DNA-Binding Proteins
  • Trans-Activators
  • Ubiquitin
  • hepatitis B virus X protein
  • Proteasome Endopeptidase Complex