Fiche publication
Date publication
juin 2020
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
,
Dr LUPBERGER Joachim
,
Pr PESSAUX Patrick
,
Dr VERRIER Eloi
Tous les auteurs :
Eller C, Heydmann L, Colpitts CC, El Saghire H, Piccioni F, Jühling F, Majzoub K, Pons C, Bach C, Lucifora J, Lupberger J, Nassal M, Cowley GS, Fujiwara N, Hsieh SY, Hoshida Y, Felli E, Pessaux P, Sureau C, Schuster C, Root DE, Verrier ER, Baumert TF
Lien Pubmed
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.
Référence
Nat Commun. 2020 Jun 1;11(1):2707
