Skip to Main content Skip to Navigation
Journal articles

Differential regulation of the Wnt/β-catenin pathway by hepatitis C virus recombinants expressing core from various genotypes

Abstract : Clinical studies have suggested association of some hepatitis C virus (HCV) subtypes or isolates with progression toward hepatocellular carcinoma (HCC). HCV core protein has been reported to interfere with host Wnt/β-catenin pathway, a cell fate-determining pathway, which plays a major role in HCC. Here, we investigated the impact of HCV core genetic variability in the dysregulation of Wnt/β-catenin pathway. We used both transient expression of core proteins from clinical isolates of HCV subtypes 1a (Cambodia), 4a (Romania) and 4f (Cameroon) and infection systems based on a set of engineered intergenotypic recombinant viruses encoding core from these various clinical strains. We found that TCF transcription factor-dependent reporter activity was upregulated by core in a strain-specific manner. We documented core sequence-specific transcriptional upregulation of several β-catenin downstream target genes associated with cell proliferation and malignant transformation, fibrogenesis or fat accumulation. The extent of β-catenin nuclear translocation varied in accordance with β-catenin downstream gene upregulation in infected cells. Pairwise comparisons of subgenotypic core recombinants and mutated core variants unveiled the critical role of core residues 64 and 71 in these dysregulations. In conclusion, this work identified natural core polymorphisms involved in HCV strain-specific activation of Wnt/β-catenin pathway in relevant infection systems.
Document type :
Journal articles
Complete list of metadatas

Cited literature [58 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-02896787
Contributor : Annette Martin <>
Submitted on : Friday, July 10, 2020 - 6:13:16 PM
Last modification on : Wednesday, October 14, 2020 - 4:15:28 AM

File

Differential regulation of the...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Stephanie Aicher, Athanasios Kakkanas, Lisette Cohen, Brigitte Blumen, Gabriela Oprisan, et al.. Differential regulation of the Wnt/β-catenin pathway by hepatitis C virus recombinants expressing core from various genotypes. Scientific Reports, Nature Publishing Group, 2018, 8 (1), pp.11185. ⟨10.1038/s41598-018-29078-2⟩. ⟨pasteur-02896787⟩

Share

Metrics

Record views

61

Files downloads

64