Animal Models for Hepatitis C

  • Eva Billerbeck
  • Ype de Jong
  • Marcus Dorner
  • Cynthia de la Fuente
  • Alexander Ploss
Chapter

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.

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Eva Billerbeck
    • 1
  • Ype de Jong
    • 1
    • 2
  • Marcus Dorner
    • 1
  • Cynthia de la Fuente
    • 1
  • Alexander Ploss
    • 1
  1. 1.Laboratory of Virology and Infectious DiseaseCenter for the Study of Hepatitis C, The Rockefeller UniversityNew YorkUSA
  2. 2.Division of Gastroenterology and HepatologyCenter for the Study of Hepatitis C, Weill Cornell Medical CollegeNew YorkUSA

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