Mutations dans la région précore du virus de l’hépatite B et fibrose hépatique : approche épidémiologique et application fondamentale

Abstract : The hepatitis B virus (HBV) infection remains a significant public health problem with more than 880 000 deaths every year worldwide. At the stage of chronic HBV infection, complications can occur such as fibrosis, cirrhosis and hepatocellular carcinoma. The role of HBV, its protein and its genomic variability in fibrosis are still unclear. Meta-analysis seems to indicate a strong link between the double mutation A1762T/G1764A detection in the basal core promotor (BCP) of HBV and the development of fibrosis. In this context, our work aimed to explore: i. the implication of BCP or precore (PC) regions mutations on the severity of fibrosis, and ii. the role of HBc and HBe proteins in fibrosis induction. For the first approach, our studies confirmed the association between the presence of the BCP double mutation and severe fibrosis, independently of the viral genotype. We also showed that the G1899A mutation in the PC region presents an antagonist effect regarding the double BCP mutant for fibrosis severity. In the second part of our work, we developed an innovative technology to produce protein via the transduction of HepaRG cells using lentiviral technology with a plasmid vector containing GFP (greenfluorescent protein) sequence. We also obtained lentiviral particles containing the wild and mutated sequences for the BCP and PC regions, in order to produce HBc and HBeprotein in HepaRG cells and to explore of the pathogenic role of BCP and PC mutants.
Document type :
Theses
Complete list of metadatas

Cited literature [171 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-02191498
Contributor : Abes Star <>
Submitted on : Tuesday, July 23, 2019 - 3:06:23 PM
Last modification on : Wednesday, July 24, 2019 - 1:33:19 AM

File

PIVERT.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-02191498, version 1

Citation

Adeline Pivert. Mutations dans la région précore du virus de l’hépatite B et fibrose hépatique : approche épidémiologique et application fondamentale. Médecine humaine et pathologie. Université d'Angers, 2017. Français. ⟨NNT : 2017ANGE0075⟩. ⟨tel-02191498⟩

Share

Metrics

Record views

35

Files downloads

22