pp 1-28 | Cite as

The Hepatitis C Virus Replicon System and Its Role in Drug Development

  • Ralf BartenschlagerEmail author
  • Volker Lohmann
Part of the Topics in Medicinal Chemistry book series


Infections with the hepatitis C virus (HCV) are an important medical problem as they can lead to chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The HCV genome was cloned molecularly in 1989, and around 25 years later, antiviral therapy has been established that eliminates the virus in more than 95% of infected individuals. To reach this goal, several hurdles had to be overcome, a major one having been the development of robust cell culture systems that were suitable for drug development, but also to study the individual steps of the HCV replication cycle. Here we summarize the step-by-step establishment of HCV cell culture systems with a focus on the replicon system that played a major role in the development of HCV-specific direct-acting antiviral drugs.


Antiviral therapy Direct acting antiviral drugs Drug development HCV cell culture system NS5A inhibitor Replicon 



Complementary DNA


Direct-acting antiviral


Encephalomyocarditis virus


Hepatitis B virus


Hepatitis C virus


Cell culture grown HCV


Hepatitis D virus


Human vesicle-associated membrane protein-associated protein A




Internal ribosomal entry site


Melanoma differentiation antigen 5


Mouse embryonic fibroblasts




Neomycin phosphotransferase


Nonstructural protein


Nontranslated region


Primary human hepatocytes


Phosphatidylinositol-4-phosphate kinase IIIα




RNA-dependent RNA polymerase


Replication-enhancing mutation


Retinoic acid inducible gene I


Reverse transcription-polymerase chain reaction


Virus titer-enhancing mutation



We are deeply indebted to all past and present members of our research groups, who made valuable contributions to all of our work. Studies in the authors’ laboratories were supported by the Deutsche Forschungsgemeinschaft, the German Ministry for Research and Education (BMBF), and the European Union.

Compliance with Ethical Standards

Funding Work in the authors’ laboratory has been supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung and the European Union.

Conflict of Interest

V.L. and R.B. are co-founders of ReBLikon GmbH, which holds commercial rights to hepatitis C virus replicon technology.

Ethical Approval

Work conducted in the authors’ laboratory did not involve studies with human participants or animals.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Infectious Diseases, Molecular VirologyHeidelberg UniversityHeidelbergGermany
  2. 2.Division of Virus-Associated CarcinogenesisGerman Cancer Research Center (DKFZ)HeidelbergGermany

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