Summary
The lack of a robust small-animal model for hepatitis C virus (HCV) has hindered the discovery and development of novel drug treatments for HCV infections. We developed a reproducible and easily accessible xenograft mouse efficacy model in which HCV RNA replication is accurately monitored in vivo by real-time, noninvasive, whole-body imaging of γ-irradiated SCID mice implanted with a mouse-adapted luciferase replicon-containing Huh-7 cell line. The model has been validated by demonstrating that both a small molecule NS3/4A protease inhibitor (BILN 2061) and human interferon- α (IFN-α) decreased HCV RNA replication and that treatment withdrawal resulted in a rebound in replication, which paralleled clinical outcomes in humans. The efficacy of protease inhibitor plus IFN-α demonstrated the application of the model for testing compounds in combination therapies. This robust mouse efficacy model provides a powerful tool for rapid evaluation of potential anti-HCV compounds in vivo.
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Acknowledgments
The authors would like to thank Yoko Oei, Montesa B. Pata-waran, Janine Kline, Evelyn N. Garrett, and Paul W. Hollenbach for developing the mouse model for anti-HCV drug evaluation. We appreciate the advice and support of Drs Dirk B. Mendel and Sharon L. Aukerman.
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Zhu, Q., Weiner, A.J. (2009). A Hepatitis C Virus Xenograft Mouse Efficacy Model. In: Kozlov, S.V. (eds) Inflammation and Cancer. Methods in Molecular Biology™, vol 511. Humana Press. https://doi.org/10.1007/978-1-59745-447-6_14
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DOI: https://doi.org/10.1007/978-1-59745-447-6_14
Publisher Name: Humana Press
Print ISBN: 978-1-934115-14-5
Online ISBN: 978-1-59745-447-6
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