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Animal Models for Hepatitis C

  • Chapter
Book cover Hepatitis C Virus: From Molecular Virology to Antiviral Therapy

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 369))

Abstract

Hepatitis C remains a global epidemic. Approximately 3 % of the world’s population suffers from chronic hepatitis C, which is caused by hepatitis C virus (HCV)—a positive sense, single-stranded RNA virus of the Flaviviridae family. HCV has a high propensity for establishing a chronic infection. If untreated chronic HCV carriers can develop severe liver disease including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Antiviral treatment is only partially effective, costly, and poorly tolerated. A prophylactic or therapeutic vaccine for HCV does not exist. Mechanistic studies of virus-host interactions, HCV immunity, and pathogenesis as well as the development of more effective therapies have been hampered by the lack of a suitable small animal model. Besides humans, chimpanzees are the only species that is naturally susceptible to HCV infection. While experimentation in these large primates has yielded valuable insights, ethical considerations, limited availability, genetic heterogeneity, and cost limit their utility. In search for more tractable small animal models, numerous experimental approaches have been taken to recapitulate parts of the viral life cycle and/or aspects of viral pathogenesis that will be discussed in this review. Exciting new models and improvements in established models hold promise to further elucidate our understanding of chronic HCV infection.

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Abbreviations

AAT:

Alpha-1 antitrypsin

ALT:

Alanine transaminase

CD:

Cluster of differentiation

CHV:

Canine hepacivirus

CLDN1:

Claudin 1

CTL:

Cytotoxic T lymphocyte

DAA:

Directly acting antiviral

EBV:

Epstein-Barr virus

EGFR:

Epidermal growth factor receptor

ES cell:

Embryonic stem cell

FAH:

Fumaryl acetoacetate hydrolase

Flt3-L:

Fms-like tyrosine kinase receptor-3 ligand

GBV:

George Baker virus

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HIS:

Human immune system

HLA:

Human leukocyte antigen

HSC:

Hematopoietic stem cell

HSV-TK:

Herpes simplex virus thymidine kinase

HVR1:

Hypervariable region 1

IFN:

Interferon

IL:

Interleukin

IL-2Rγnull:

Interleukin 2 receptor gamma deficient

iPSC:

Induced pluripotent stem cell

JFH:

Japanese patient with fulminant hepatitis

IRF:

Interferon regulatory factor

LDL-R:

Low density lipoprotein receptor

MAVS:

Mitochondrial antiviral signal protein

MHC:

Major histocompatibility complex

MUP:

Major urinary protein

NK:

Natural killer cell

NANB:

Non-A/non-B hepatitis

NOD:

Non-obese diabetic

NS:

Non-structural protein

NPHV:

Non-primate hepacivirus

NPC1L1:

Niemann-Pick C1-like 1

NTBC:

2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione

OCLN:

Occludin

PI4IIIα:

Phosphatidylinositol 4 kinase III alpha

PKR:

Protein kinase R

Rag:

Recombinase activating gene

SCARB1:

Scavenger recepter type B class I

SCID:

Severe combined immunodeficiency

SCF:

Stem cell factor

SIRP-α:

Signal regulatory protein alpha

SVR:

Sustained virologic response

TNF:

Tumor necrosis factor

TPO:

Thrombopoietin

uPA:

Urokinase plasminogen activator

UTR:

Untranslated region

VLDL:

Very low-density lipoprotein

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Authors and Affiliations

  1. Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, 10065, USA

    Eva Billerbeck, Ype de Jong, Marcus Dorner, Cynthia de la Fuente & Alexander Ploss

  2. Division of Gastroenterology and Hepatology, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, 10021, USA

    Ype de Jong

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  1. Eva Billerbeck
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  2. Ype de Jong
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  3. Marcus Dorner
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  4. Cynthia de la Fuente
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  5. Alexander Ploss
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Correspondence to Alexander Ploss .

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  1. Department for Infectious Diseases Molecular Virology, University of Heidelberg, Heidelberg, Germany

    Ralf Bartenschlager

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Billerbeck, E., de Jong, Y., Dorner, M., de la Fuente, C., Ploss, A. (2013). Animal Models for Hepatitis C. In: Bartenschlager, R. (eds) Hepatitis C Virus: From Molecular Virology to Antiviral Therapy. Current Topics in Microbiology and Immunology, vol 369. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27340-7_3

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