Hepatitis C Clinical Trial
Official title:
Hepatitis C 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 C virus
(HCV). HCV 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
HCV 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 HCV virions in clinical samples,
followed by the identification of their HCV-bound host proteins and the characterization of
their functions. Proteomics profiling of HCV particles purified from clinical samples will
be overlaid with proteins identified and characterized in cell culture grown HCV particles
during my post-doctoral training, using clinical biomarker discovery grade criteria. Targets
identified in both samples sets will be subjected to in vitro investigations using
HCV-replicating cells. Conventional biochemical and imaging methods will be used in order
to: (i) ascertain their physical association with HCV virions; (ii) define the modalities of
their interaction with HCV proteins; (iii) decipher the topology and subcellular
localization of their association with HCV 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.
n/a
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Basic Science
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