Scotomas in molecular virology and epidemiology of hepatitis C virus

Table 1 Summary of in vitro and in vivo models for hepatitis C virus

In vitro and in vivo models	Established year	Advantages	Deficiencies
In vitro
Cultivation of HCV	1993-1999	Achieved cultivation of HCV in human foetal liver cells, human hepatocytes or PBMC. Illustrated HCV is quite species selective and has a narrow range of hosts	Requires specific cellular factors to support viral lifecycle. Primary human and chimpanzee hepatocytes or highly differentiated cells dependent. Most of them have yielded limited success. Poor reproducibility and low levels of HCV replication
HCV replicon	1995-2000	Provided a cell-based model for the study on HCV genome replication
HCV VLP	1998-1999	Rare evidence to support that HCV structural proteins core, E1, and E2 could form VLP
HCVpp	2003	Provided a convenient and feasible tool for studies on viral entry, HCV receptor, neutralizing antibody, etc.
HCVcc	2005	A break through in production of infectious hepatitis C virus in tissue culture
In vivo
Chimpanzee	1979	The only recognized animal model for HCV study, played a critical role in HCV discovery and play an essential role in defining the natural history of HCV	Chimpanzees differ from humans in their course of infection, that chronic carriers do not develop cirrhosis or fibrosis, limited availability, cost performance, and public resistance
Tree shrew	1998	Might be a succedaneum for chimpanzees	Persistent HCV infection could not be established and only 25% of infected animals developed transient or intermittent viremia. Germ line was not available to a small animal model
Chimeric human liver mouse	2001	Exhibited prolonged infection with high viral titers following inoculation with HCV isolated from human serum. HCV can be transmitted horizontally. Drug evaluation	Since the mice were immunodeficient, they were not appropriate models to study HCV pathogenesis
Genetically humanized mouse	2011	Represents the first immunocompetent mice model for HCV study. Allows for the studies of HCV coreceptor biology in vivo	Operation is difficult

HCVpp: Hepatitis C virus (HCV) pseudotyped viral particles; VLP: Virus like particle; HCVcc: Cell culture derived HCV.