HCV Virions Bound Proteins

NCT02795403 | Completed

• 1 other identifier: 2009-596
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis C

Keywords

HCV, liver

Outcome Measures

Primary Outcomes (3)

• Qualitative identification (unit used: Protein Prophet score) of a given virion-bound protein in purified virions preparations

  Protein prophet scores allow one to estimate the robustness of identification of a given protein in MS approaches.

  One to two years after mass spectrometry identification of the candidate

• Quantitative evaluation of its implication in viral morphogenesis (unit used: TCID50).

  TCID50 units are infectivity units routinely used in HCV research for viral infectivity quantification.

  One to two years after mass spectrometry identification of the candidate

• Quantitative evaluation of viral entry (unit used: HCV RNA /GUS mRNA copy ratios).

  HCV RNA /GUS mRNA copy ratios are derived from the 2\^delta(delta Ct) method.

  One to two years after mass spectrometry identification of the candidate

Secondary Outcomes (1)

• Comparison of clinical virions datasets with in vitro grown virions datasets

  One to two years after mass spectrometry identification of the candidate

Study Arms (2)

Viraemic

EXPERIMENTAL

Other: blood draw of 150ml, twice

responder group

EXPERIMENTAL

Other: blood draw of 150ml, twice

Interventions

blood draw of 150ml, twice OTHER

Viraemic; responder group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult\> 18 and \<60 years
• Infected with HCV genotype 1 HCV antibody positive.
• positive viremia for more than 6 months
• Viremia\> 106 IU / ml.
• nonresponders to previous treatment and without antiviral treatment for 2 months.
• For control samples: Patients responders to previous treatment and without antiviral treatment for 2 months.

You may not qualify if:

• Patient receiving or having received antiviral treatment within two months.
• patient with against-indication for a blood sample of 150 ml
• immunosuppressive therapy patient
• Patient with liver disease other than hepatitis C.
• Patients with cirrhosis.
• patient with hepatocellular carcinoma.
• Patients with one or more severe co-morbidities defined as:
• Co-infection with HIV or HBV.
• hematological malignancies changing or aplasia
• Insulin-dependent diabetes
• dialyzed chronic renal failure
• Heart failure
• Persons subject to legal protection or the subject of a safeguard measure of justice not affiliated with a social security scheme or not beneficiaries of such a scheme
• Pregnant women

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Service d'Hépato-Gastroentérologie Lyon Croix-Rousse Hospices Civils de Lyon

Lyon, 69004, France

Location

Related Publications (1)

• Cottarel J, Plissonnier ML, Kullolli M, Pitteri S, Clement S, Millarte V, Si-Ahmed SN, Farhan H, Zoulim F, Parent R. FIG4 is a hepatitis C virus particle-bound protein implicated in virion morphogenesis and infectivity with cholesteryl ester modulation potential. J Gen Virol. 2016 Jan;97(1):69-81. doi: 10.1099/jgv.0.000331. Epub 2015 Oct 29.

  PMID: 26519381 BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Fabien ZOULIM, MD

  Service d'Hépato-Gastroentérologie Lyon Croix-Rousse Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: June 10, 2016
• Study Start: January 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)