Hepatitis B Virus Infection
Conditions
Keywords
HBV, liver
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 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.
Interventions
OTHERblood draw
blood draw of 150ml, twice
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria * Adult\> 18 and \<60 years * Infected with HBV. * positive viremia for more than 6 months * Viremia\> 106 IU / ml. * Immunotolerant individuals, untreated * Aviraemic individuals,
Exclusion criteria
* patient with against-indication for a blood sample of 150 ml * immunosuppressive therapy patient * Patient with liver disease other than hepatitis B. * patient with hepatocellular carcinoma. * Patients with one or more severe co-morbidities defined as: * Co-infection with HIV or hepatitis C virus (HCV). * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Presence of a virion-bound protein identified by mass spectrometry | One to two years after mass spectrometry identification of the candidate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of clinical virions datasets with in vitro grown virions datasets (mass spectrometry) | 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 origin. |
Countries
France
Outcome results
None listed