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Hepatitis C virus cell entry: a target for novel antiviral strategies to address limitations of direct acting antivirals

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Abstract

Hepatitis C virus (HCV) infection remains a major global health problem, with 130–170 million chronically infected individuals at risk to develop severe liver disease, including hepatocellular carcinoma. Although the development of direct-acting antivirals offers cure for a large majority of patients, there are still a number of clinical challenges. These include DAA failure in a significant subset of patients, difficult-to-treat genotypes and limited access to therapy due to high costs. Moreover, recent data indicate that the risk for liver cancer persists in patients with advanced fibrosis. These challenges highlight the need for continued efforts towards novel therapeutic strategies for HCV. Over the past two decades, advances in HCV model systems have enabled a detailed understanding of HCV entry and its clinical impact. Many of the virus-host interactions involved in HCV entry have now been identified and explored as antiviral targets. Furthermore, viral entry is recognized as an important factor for graft reinfection and establishment of persistent infection. HCV entry inhibitors, therefore, offer promising opportunities to address the limitations of DAAs. Here, we summarize recent advances in the field of HCV entry and discuss perspectives towards the prevention and cure of HCV infection and virus-induced liver disease.

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Acknowledgements

T.F.B. acknowledges support through funding by the European Union (ERC-2008-AdG-HEPCENT, ERC-2014-AdG-HEPCIR, FP7 HepaMAb, H2020 HEPCAR and Interreg IV FEDER-Hepato-Regio-Net 2012), the Agence Nationale de Recherches sur le SIDA (ANRS), the Direction Générale de l’Offre de Soins (A12027MS), Inserm and the University of Strasbourg Foundation. This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and benefits from funding from the state managed by the French National Research Agency as part of the Investments for the future program. C.C.C. is supported by a fellowship from the Canadian Institutes of Health Research (201411MFE- 338606-245517).

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  1. Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 3 Rue Koeberlé, 67000, Strasbourg, France

    Che C. Colpitts & Thomas F. Baumert

  2. Université de Strasbourg, 67000, Strasbourg, France

    Che C. Colpitts & Thomas F. Baumert

  3. Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, 67000, Strasbourg, France

    Thomas F. Baumert

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C.C.C. and T.F.B. declare no conflict of interest. T.F.B. has served as an advisor on HCV antivirals for Biotest, Gilead and Vironexx. T.F.B is a co-inventor on a US patent on anti-Claudin-1 antibody for prevention and treatment of HCV infection filed by Inserm, University of Strasbourg and Genovac/Aldevron.

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Colpitts, C.C., Baumert, T.F. Hepatitis C virus cell entry: a target for novel antiviral strategies to address limitations of direct acting antivirals. Hepatol Int 10, 741–748 (2016). https://doi.org/10.1007/s12072-016-9724-7

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