HCV Virions Bound Proteins
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|ClinicalTrials.gov Identifier: NCT02795403|
Recruitment Status : Completed
First Posted : June 10, 2016
Last Update Posted : June 10, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatitis C||Other: blood draw of 150ml, twice||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Primary Purpose:||Basic Science|
|Official Title:||Hepatitis C Virus Particles-bound Human Proteins : Identification in Clinical Samples and Implication in the Viral Life Cycle|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||July 2015|
|Actual Study Completion Date :||July 2015|
Other: blood draw of 150ml, twice
|Experimental: responder group||
Other: blood draw of 150ml, twice
- Qualitative identification (unit used: Protein Prophet score) of a given virion-bound protein in purified virions preparations [ Time Frame: One to two years after mass spectrometry identification of the candidate ]Protein prophet scores allow one to estimate the robustness of identification of a given protein in MS approaches.
- Quantitative evaluation of its implication in viral morphogenesis (unit used: TCID50). [ Time Frame: One to two years after mass spectrometry identification of the candidate ]TCID50 units are infectivity units routinely used in HCV research for viral infectivity quantification.
- Quantitative evaluation of viral entry (unit used: HCV RNA /GUS mRNA copy ratios). [ Time Frame: One to two years after mass spectrometry identification of the candidate ]HCV RNA /GUS mRNA copy ratios are derived from the 2^delta(delta Ct) method.
- Comparison of clinical virions datasets with in vitro grown virions datasets [ Time Frame: One to two years after mass spectrometry identification of the candidate ]Proteins identified from viral particles purified from clinical samples will be compared to proteins identified in viral particles from cells of human hepatocarcinoma (Huh7.5) infected with HCV and from which data are published.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02795403
|Service d'Hépato-Gastroentérologie Lyon Croix-Rousse Hospices Civils de Lyon|
|Lyon, France, 69004|
|Principal Investigator:||Fabien ZOULIM, MD||Service d'Hépato-Gastroentérologie Lyon Croix-Rousse Hospices Civils de Lyon|