Expression of the hepatitis B virus (HBV) accessory protein HBx is a requirement for viral replication. In this thesis, we
investigated how HBx supports HBV replication, and we performed studies to identify its function. In chapter 2 we show that
the overlap of reading frames in the HBV genome restricts viral evolution and affects the mutation rate. The mutation rate
varied and correlated negatively with viral load. Because no crystallography-based tertiary structure of HBx is available,
we have predicted the tertiary structure by ab initio computer modelling in chapter 3. Our model shows that HBx seems to have
significant structural homology with the human thymine DNA glycosylase (TDG). In chapter 4 we show that HBx inhibits TDG-initiated
DNA repair. Amongst the HBx interacting proteins described in the literature are various epigenetic modulators. The data we
present in chapter 5 show that an important class of these proteins, the histone deacetylases, indeed suppress HBV replication,
but that their activity is not affected by HBx. Therefore we applied subtractive mass spectrometry to systematically identify
relevant HBx interacting proteins. As described in chapter 6, we identified one HBx interacting protein, talin-1, which was
targeted for proteasomal degradation by HBx. Subsequent analysis revealed that talin-1 is a viral restriction factor, and
that HBV replication critically depends on HBx-mediated talin-1 degradation. In chapter 7, we explored the possibility to
target HBV transcription in HBx dependent- and independent ways. By screening 640 FDA approved drugs, we identified compounds
that suppressed HBV replication by targeting HBV RNA transcription.
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let
the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible
and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands.
You will be contacted as soon as possible.