Abstract
The development of causal therapies depends on the availability of systems to determine the inhibitory capacity of a compound. As viruses are obligate intracellular parasites, the efficacy of an antiviral drug is usually evaluated in a cell-culture system. Unfortunately, the hepatitis C virus, the principal causative agent of acute and chronic liver disease, cannot be propagated efficiently in the laboratory. However, the recent development of a replicon system opens up an encouraging possibility for drug discovery.
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Acknowledgements
I thank all the members of my laboratory for helpful and stimulating discussions, and M. Frese, V. Lohmann, T. Pietschmann and S. Sparacio for a critical reading of the manuscript. I also thank J. Bukh, O. Flores, B. Gu, S. Lemon and C. M. Rice for sharing data before publication. My apologies to all the scientists whose work and discoveries I could not refer to and cite because of space limitations. The work carried out in my laboratory was supported by grants from the European Union and the Deutsche Forschungsgemeinschaft.
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Glossary
- ACTINOMYCIN D
-
A drug that selectively blocks RNA synthesis from DNA but not RNA templates. Therefore, replication of positive-strand RNA genomes that is mediated by an RdRp continues in infected cells, whereas transcription of cellular genes is blocked.
- BICISTRONIC REPLICON
-
Consists of two cistrons, one translated under the control of the HCV IRES and the second one under the control of a heterologous IRES element. We used the IRES of the encephalomyocarditis virus because this element is efficient in a broad range of cell lines, and is well studied.
- CISTRON
-
In this case, refers to a genetic unit that is expressed as a single protein.
- NEGATIVE-STRAND RNA
-
Generated during RNA replication and — as far as we know — does not code for viral proteins.
- POSITIVE-STRAND RNA
-
Has the same polarity as cellular messenger RNA and can therefore be used directly for the expression of a protein. Viruses that have genomes with this property are classified as positive-strand RNA viruses. HCV is one member of this class. The complement is a negative-strand RNA.
- REPLICON
-
A genetic element that can replicate under its own control in a cell. Such an element can be DNA (for example, a plasmid) or RNA.
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Bartenschlager, R. Hepatitis C virus replicons: potential role for drug development. Nat Rev Drug Discov 1, 911–916 (2002). https://doi.org/10.1038/nrd942
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DOI: https://doi.org/10.1038/nrd942
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