| Autor: |
Eller, C. (Carla), Heydmann, L. (Laura), Colpitts, C. (Che) C. (C), El Saghire, H. (Houssein), Piccioni, F. (Federica), Jühling, F. (Frank), Majzoub, K. (Karim), Pons, C. (Caroline), Bach, C. (Charlotte), Lucifora, J. (Julie), Lupberger, J. (Joachim), Nassal, M. (Michael), Cowley, Glenn S.S. (S), Fujiwara, N. (Naoto), Hsieh, S. (Sen-Yung) Y. (Y), Hoshida, Y. (Yujin), Felli, E. (Emanuele), Pessaux, P. (Patrick), Sureau, C. (Camille), Schuster, C. (Catherine), Root, David E.E. (E), Verrier, E. (Eloi) R. (R), Baumert, Thomas F.F. (F) |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
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. the IHU Fondation ARC (French Cancer Agency) TheraHCC program IHU201301187 and IHU201901299, the Institut Universitaire de France and the Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R03AI131066. C.C.C. acknowledges fellowships from the Canadian Institutes of Health Research (201411MFE-338606-245517) and the Canadian Network on Hepatitis C.E.R.V. acknowledges fellowship from ANRS (ECTZ50121). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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