Hepatitis B Virus Infection Clinical Trial
Official title:
Hepatitis B Virus Particles-bound Human Proteins : Identification in Clinical Samples and Implication in the Viral Life Cycle
The emergence of hepatocellular carcinoma (HCC) has prompted a search for a thorough
understanding of the biology of one of its major causative agents, the hepatitis B virus
(HBV). HBV particles acquire via budding and encapsidation cellular proteins. There is
mounting evidence on several viral species that virion-bound proteins are prone to be
involved either at the replication, budding/egress or entry/release steps of the viral cycle.
Identifying such targets may yield ideal candidates for gaining insight on the dependence of
HBV upon a restricted subset of host proteins, therefore providing refined sets of
genetically stable targets for therapy. This project's goals are to set up adequate
conditions for robust and reproducible purification of HBV virions in clinical samples,
followed by the identification of their HBV-bound host proteins and the characterization of
their functions. Proteomics profiling of HBV particles purified from clinical samples will be
overlaid with proteins identified and characterized in cell culture grown HBV particles,
using clinical biomarker discovery grade criteria. Targets identified in both samples sets
will be subjected to in vitro investigations using HBV-replicating cells. Conventional
biochemical and imaging methods will be used in order to: (i) ascertain their physical
association with HBV virions; (ii) define the modalities of their interaction with HBV
proteins; (iii) decipher the topology and subcellular localization of their association with
HBV proteins and virions; (iv) quantitatively assess their functional involvement in particle
budding, egress or secretion and infectivity. A candidate that yielded satisfactory results
in these experiments will be disclosed and further investigated at the level of structural
biology, in collaborative research programs.
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