Cell Culture Systems for Hepatitis C Virus

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

Abstract

Due to the obligatory intracellular lifestyle of viruses, cell culture systems for efficient viral propagation are crucial to obtain a detailed understanding of the virus–host cell interaction. For hepatitis C virus (HCV) the development of permissive and authentic culture models continues to be a challenging task. The first efforts to culture HCV had limited success and range back to before the virus was molecularly cloned in 1989. Since then several major breakthroughs have gradually overcome limitations in culturing the virus and sequentially permitted analysis of viral RNA replication, cell entry, and ultimately the complete replication cycle in cultured cells in 2005. Until today, basic and applied HCV research greatly benefit from these tremendous efforts which spurred multiple complementary cell-based model systems for distinct steps of the HCV replication cycle. When used in combination they now permit deep insights into the fascinating biology of HCV and its interplay with the host cell. In fact, drug development has been much facilitated and our understanding of the molecular determinants of HCV replication has grown in parallel to these advances. Building on this groundwork and further refining our cellular models to better mimic the architecture, polarization and differentiation of natural hepatocytes should reveal novel unique aspects of HCV replication. Ultimately, models to culture primary HCV isolates across all genotypes may teach us important new lessons about viral functional adaptations that have evolved in exchange with its human host and that may explain the variable natural course of hepatitis C.

Keywords

Primary Human Hepatocyte Subgenomic Replicon Chimeric Genome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

BMEC

Brain microvascular endothelial cells

CNS

Central nervous system

Con1

Consensus genome 1

DAA

Direct acting antiviral

DC-SIGN

Dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin

EGFR

Epidermal growth factor receptor

EMCV

Encephalomyocarditis virus

EphA2

Ephrin receptor A2

GFP

Green fluorescent protein

HCV

Hepatitis C virus

HCVTCP

Hepatitis C virus trans-complemented particles

HBV

Hepatitis B virus

HIV

Human immunodeficiency virus

iPSC

Induced pluripotent stem cells

IRES

Internal ribosomal entry site

JFH1

Japanese fulminant hepatitis

LDL-R

Low-density lipoprotein receptor

MEF

Mouse embryonic fibroblasts

MPCC

Micropattern co-cultures

mL

Milliliter

MLV

Murine leukemia virus

NPC1L1

Niemann-Pick C1-like cholesterol adsorption receptor

PBMC

Peripheral blood mononuclear cells

PHH

Primary human hepatocytes

REM

Replication enhancing mutations

RIG-I

Retinoic acid-inducible gene I

SEAP

Secreted embryonic alkaline phosphatase

siRNA

small interfering RNAs

TCID50

Tissue culture infectious dose 50

VSV

Vesicular stomatitis virus

Notes

Acknowledgments

The authors thank Gisa Gerold for critical reading of the manuscript and Dorothea Bankwitz for helping with the preparation of the figures. Work in the authors’ laboratory is supported by grants from the European Research Council (VIRAFRONT), the Deutsche Forschungsgemeinschaft (DFG) (SFB 900, Teilprojekt A6; PI 734/1-1 and PI734/2-1), and by grants from the Initiative and Networking Fund of the Helmholtz Association SO-024 and HA-202 to T.P. E.S. is supported by DFG (STE 1954/1-1).

Financial and competing interest disclosure The authors declare no conflict of interest. T.P. has received consulting fees from Biotest AG and from Janssen Global Services, LLC.

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Division of Experimental VirologyTWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)HannoverGermany

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