Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication

Virology. 2012 Apr 25;426(1):73-82. doi: 10.1016/j.virol.2012.01.021. Epub 2012 Feb 17.


Robust hepatitis B virus (HBV) replication is stimulated by the regulatory HBx protein. HBx binds the cellular protein DDB1; however, the importance of this interaction for HBV replication remains unknown. We tested whether HBx binding to DDB1 was required for HBV replication using a plasmid based replication assay in HepG2 cells. Three DDB1 binding-deficient HBx point mutants (HBx(69), HBx(90/91), HBx(R96E)) failed to restore wildtype levels of replication from an HBx-deficient plasmid, which established the importance of the HBx-DDB1 interaction for maximal HBV replication. Analysis of overlapping HBx truncation mutants revealed that both the HBx-DDB1 binding domain and the carboxyl region are required for maximal HBV replication both in vitro and in vivo, suggesting the HBx-DDB1 interaction recruits regulatory functions critical for replication. Finally we demonstrate that HBx localizes to the Cul4A-DDB1 complex, and discuss the possible implications for models of HBV replication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Hep G2 Cells
  • Hepatitis B / metabolism*
  • Hepatitis B / virology
  • Hepatitis B virus / chemistry
  • Hepatitis B virus / genetics
  • Hepatitis B virus / physiology*
  • Humans
  • Protein Binding
  • Protein Structure, Tertiary
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Viral Regulatory and Accessory Proteins
  • Virus Replication*


  • DDB1 protein, human
  • DNA-Binding Proteins
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein