Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication |
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Authors: | Hodgson Amanda J Hyser Joseph M Keasler Victor V Cang Yong Slagle Betty L |
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Affiliation: | a Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USAb Signal Transduction Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA |
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Abstract: | 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 (HBx69, HBx90/91, HBxR96E) 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. |
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Keywords: | Hepatitis B virus HBx DDB1 HBV replication |
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