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

Carla Eller, Laura Heydmann, Che C. Colpitts, Houssein El Saghire, Federica Piccioni, Frank Jühling, Karim Majzoub, Caroline Pons, Charlotte Bach, Julie Lucifora, Joachim Lupberger, Michael Nassal, Glenn S. Cowley, Naoto Fujiwara, Sen Yung Hsieh, Yujin Hoshida, Emanuele Felli, Patrick Pessaux, Camille Sureau, Catherine SchusterDavid E. Root, Eloi R. Verrier, Thomas F. Baumert

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number2707
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Eller, C., Heydmann, L., Colpitts, C. C., El Saghire, H., Piccioni, F., Jühling, F., Majzoub, K., Pons, C., Bach, C., Lucifora, J., Lupberger, J., Nassal, M., Cowley, G. S., Fujiwara, N., Hsieh, S. Y., Hoshida, Y., Felli, E., Pessaux, P., Sureau, C., ... Baumert, T. F. (2020). A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor. Nature communications, 11(1), [2707]. https://doi.org/10.1038/s41467-020-16517-w