Hepatitis C pp 361-372 | Cite as

Adaptation of the Hepatitis C Virus to Cell Culture

  • Artur Kaul
  • Ilka Wörz
  • Ralf Bartenschlager
Part of the Methods in Molecular Biology™ book series (MIMB, volume 510)

Abstract

A major breakthrough in the field of HCV research was the development of a system that supports the production of infectious virus particles. The key to this achievement was the molecular cloning of a genotype 2a genome, designated JFH1, which replicates to exceptionally high levels and at the same time supports virus particle assembly and release. A major drawback of this system was, however, the rather low yield of infectious particles obtained with the JFH1 genome as well as with most JFH1-derived virus chimeras. One approach to overcoming this hurdle is adaptation of the HCV genomes to cell culture. We found that both JFH1 and all chimeras, except one, can easily be adapted to cultured cells, increasing virus yields by up to three orders of magnitude. Surprisingly, adaptation is achieved by a multitude of mutations residing in both the structural and the nonstructural proteins. We therefore argue that a complex interaction between structural proteins and the HCV replicase takes place to allow efficient virus particle production.

Key Words

Cell-culture adaptation HCV adaptation adaptive mutations virus production Huh-7 cells nonstructural proteins 

Notes

Acknowledgments

This work was supported by grants of the German Research Council (SFB 638, Teilprojekt A5 and BA 1505/2-1).

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Artur Kaul
    • 1
  • Ilka Wörz
    • 1
  • Ralf Bartenschlager
    • 1
  1. 1.Department of Molecular VirologyUniversity of HeidelbergHeidelbergGermany

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