In Vitro Systems for the Study of Hepatitis C Virus Infection

Table 1

Culture models to study the HCV lifecycle. Several hepatic models have been employed to study diverse aspects of the viral lifecycle. Models of nonhepatic origin have also been employed and proved useful in identifying potential extra hepatic sites of HCV infection in vivo. In addition, Caco2 cells were used to study the effects of polarity on HCV infection as most hepatic cell lines fail to polarize in culture. However, a perfect model that closely mimics the in vivo environment is still yet to be identified.

Cell type	Tissue	HCV lifecycle	Reference	Comment
Immortalized cell lines
Huh 6/Claudin-1	Hepatoblastoma	Entry/replication	[58, 59]	Interferon resistance
Huh-7	HCC	Full lifecycle	[14]	Interferon response to infection
Huh-7.5	HCC	Full lifecycle	[14]	Defective RIG-I pathway
Hep3B	HCC	Entry	[57, 63]	Limited HCV replication
HepG2-CD81	Hepatoblastoma	Entry/replication	[64–66]	Forms hepatic polarity
PLC/PRF/5	Primary liver carcinoma	Entry	[57, 60]	Low HCV replication
293-T/Claudin-1	Kidney	Entry/replication	[11]	Non-hepatic origin
hCMEC/D3	Brain endothelia	Entry/replication	[67]	In vitro study of HCV neuropathology
HBMEC	Brain endothelia	Entry/replication	[67]	In vitro study of HCV neuropathology
SK-N-MC	Neuroepithelioma	Entry	[68]	Low virus replication
SK-PN-DW	Neuroepithelioma	Entry	[68]	Low virus replication
Caco2	Colorectal adenocarcinoma	Entry/replication	[69]	Non-hepatic origin; Demonstrates epithelial polarity
Primary cell culture
Primary hepatocytes	Human liver	Full lifecycle	[38, 42, 70]	Limited access to liver tissue, physiologically relevant model
Fetal hepatocytes	Human liver	Entry/replication	[47–49]	Limited access to liver tissue, antiviral response to infection
Chimpanzee hepatocytes	Chimp liver	Replication	[36]	Limited availability
Stem cell derived hepatocytes	Human embryo	Full life cycle	[43, 44, 46]	Highly differentiated, supports HCV life cycle