A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2020

A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor

Résumé

Chronic HBV infection is a major cause of liver disease and cancer worldwide. Approaches for cure are lacking, and the knowledge of virus-host interactions is still limited. Here, we perform a genome-wide gain-of-function screen using a poorly permissive hepatoma cell line to uncover host factors enhancing HBV infection. Validation studies in primary human hepatocytes identified CDKN2C as an important host factor for HBV replication. CDKN2C is overexpressed in highly permissive cells and HBV-infected patients. Mechanistic studies show a role for CDKN2C in inducing cell cycle G1 arrest through inhibition of CDK4/6 associated with the upregulation of HBV transcription enhancers. A correlation between CDKN2C expression and disease progression in HBV-infected patients suggests a role in HBV-induced liver disease. Taken together, we identify a previously undiscovered clinically relevant HBV host factor, allowing the development of improved infectious model systems for drug discovery and the study of the HBV life cycle.
Fichier principal
Vignette du fichier
s41467-020-16517-w.pdf (3 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

inserm-02879963 , version 1 (24-06-2020)

Identifiants

Citer

Carla Eller, Laura Heydmann, Che C Colpitts, Houssein El Saghire, Federica Piccioni, et al.. A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor. Nature Communications, 2020, 11 (1), pp.2707. ⟨10.1038/s41467-020-16517-w⟩. ⟨inserm-02879963⟩
144 Consultations
105 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More