Mouse Systems to Model Hepatitis C Virus Treatment and Associated Resistance

Abstract
While addition of the first-approved protease inhibitors (PIs), telaprevir and boceprevir, to pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy significantly increased sustained virologic response (SVR) rates, PI-based triple therapy for the treatment of chronic hepatitis C virus (HCV) infection was prone to the emergence of resistant viral variants. Meanwhile, multiple direct acting antiviral agents (DAAs) targeting either the HCV NS3/4A protease, NS5A or NS5B polymerase have been approved and these have varying potencies and distinct propensities to provoke resistance. The pre-clinical in vivo assessment of drug efficacy and resistant variant emergence underwent a great evolution over the last decade. This field had long been hampered by the lack of suitable small animal models that robustly support the entire HCV life cycle. In particular, chimeric mice with humanized livers (humanized mice) and chimpanzees have been instrumental for studying HCV inhibitors and the evolution of drug resistance. In this review, we present the different in vivo HCV infection models and discuss their applicability to assess HCV therapy response and emergence of resistant variants.
Keywords: HCV; animal models; therapy; direct acting antiviral agents; humanized mice; resistance; deep sequencing
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Share & Cite This Article
Further Mendeley | CiteULike
Export to BibTeX | EndNote | RIS
MDPI and ACS Style

Mesalam, A.A.; Vercauteren, K.; Meuleman, P. Mouse Systems to Model Hepatitis C Virus Treatment and Associated Resistance. Viruses 2016, 8, 176.
View more citation formats   

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
Related Articles

    Resistance patterns associated with HCV NS5A inhibitors provide limited insight into drug binding.
    Moheshwarnath Issur et al., Viruses, 2014
    Faldaprevir for the Treatment of Hepatitis C
    Kanda, Tatsuo ; Yokosuka, Osamu ; Omata, Masao et al., Int J Mol Sci, 2015
    Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance
    Eltahla, Auda A.; Luciani, Fabio ; White, Peter A.; Lloyd, Andrew R.; Bull, Rowena A. et al., Viruses, 2015
    Interferon-Free Hepatitis C Treatment before and after Liver Transplantation: The Role of HCV Drug Resistance
    Roche, Bruno ; Coilly, Audrey ; Roque-Afonso, Anne-Marie ; Samuel, Didier et al., Viruses, 2015

    Decision Support in Medicine: Renal Cell Carcinoma
    The Oncology Practice, 2016
    First comorbidity guidelines drafted for psoriatic arthritis
    By: Ted Bosworth, Dermatology News Digital Network, Dermatology News
    Screen all psoriasis patients for hepatitis before immunosuppressive therapy
    By: Bruce Jancin, Dermatology News Digital Network, Dermatology News
    FDA Approves Omacetaxine for Chronic Myeloid Leukemia
    By: Elizabeth Mechcatie, Oncology Practice Digital Network, The Oncology Practice, 2012

Powered by TrendMD
Article Metrics
Article access statisticsFull-Text ViewsAbstract Views22. Jun23. Jun24. Jun25. Jun26. Jun27. Jun28. Jun29. Jun30. Jun1. Jul2. Jul3. Jul4. Jul5. Jul6. Jul7. Jul8. Jul9. Jul10. Jul0501001502007. JulSum: 90Daily views: 5

Notes: Multiple requests from the same IP address are counted as one view.