Medical Microbiology and Immunology

, Volume 208, Issue 1, pp 3–24 | Cite as

Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development

  • Volker LohmannEmail author


Chronic hepatitis C virus (HCV) infections affect 71 million people worldwide, often resulting in severe liver damage. Since 2014 highly efficient therapies based on directly acting antivirals (DAAs) are available, offering cure rates of almost 100%, if the infection is diagnosed in time. It took more than a decade to discover HCV in 1989 and another decade to establish a cell culture model. This review provides a personal view on the importance of HCV cell culture models, particularly the replicon system, in the process of therapy development, from drug screening to understanding of mode of action and resistance, with a special emphasis on the contributions of Ralf Bartenschlager’s group. It summarizes the tremendous efforts of scientists in academia and industry required to achieve efficient DAAs, focusing on the main targets, protease, polymerase and NS5A. It furthermore underpins the importance of strong basic research laying the ground for translational medicine.


Hepatitis C virus HCV Hepatocyte DAA Therapy Antiviral Cell culture Replicon Genotype Bartenschlager Adaptation 



I would like to particularly thank Thomas Pietschmann, Sandra Buehler and Ilka Rebhan for critical reading of the manuscript. Work in the author’s laboratory is supported by grants from the Deutsche Forschungsgemeinschaft (LO 1556/4-1, TRR179 TP17 and TRR209, TP A2). A special focus of this review is on the contribution of Ralf Bartenschlager and his team to the development of HCV cell culture models and antiviral therapies, on occasion of his 60th birthday in 2018. I, therefore, apologize for not comprehensively citing all relevant literature at some points.

Compliance with ethical standards

Conflict of interest

Volker Lohmann is co-owner of Reblikon GmbH, a company licensing the replicon system for commercial purposes.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Infectious Diseases, Molecular Virology, Centre for Integrative Infectious Disease Research (CIID)University of HeidelbergHeidelbergGermany

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