Table 1.

Cell culture systems and in vitro models developed to study hepatitis B virus and hepatitis C virus envelope glycoproteins

	In vitro model/cell culture system	Step of the viral cycle	Benefits and major findings	Drawbacks
HBV	Primary hepatocyte cultures			Not easy to handle
	PHH	Replication	No need for DMSO and hydrocortisone for PTH system	Cells cannot be propagated in vitro
	PTH			Addition of growth factors
	Hepatic cell lines
	HepG2	Binding and infection	Specific binding and uptake	No productive infection
	HepaRG	(HBV and HDV)	Cellular determinants of hepatocyte differentiation and their influence on HBV infection	Addition of DMSO and hydrocortisone
HCV	Recombinant E2 glycoprotein: Truncated soluble form of recombinant E2 glycoprotein	Entry process	Identification of two major receptors CD81 and SR-BI	Different behavior from E1 E2 heterodimers
			Interaction with heparan sulfate proteoglycans	Binding to various cell lines different from hepatocytes
	VLPs: Self assembly of HCV structural proteins produced in insect or mammalian cells using a recombinant virus	Entry process	E1–E2 heterodimers at virion surface	Difference in glycosylation status
			Cell attachment	Difficult to prepare
			Attractive vaccine candidate	Non replicative
	HCVpp: Unmodified HCV envelope glycoproteins assembled onto retroviral or lentiviral core particles	Entry process	Study of infectivity and neutralization	Only the very early steps of viral cycle
				No association with lipoproteins
				No budding at the ER
	HCVcc: Transfection of one HCV strain sequence (JFH1) from a Japanese patient with fulminant hepatitis, in Huh 7 cell line.	Entire life cycle	Entry process +++	Restricted to Huh-7 cell line
			Replication	Restricted to JFH1 non structural proteins sequence
			Virus production
			Screening of antiviral molecules

HBV: Hepatitis B virus; HCV: Hepatitis C virus; VLP: Virus-like particles; HCVpp: HCV pseudotype particles; HCVcc: Cell culture derived HCV; HDV: Hepatitis D virus; DMSO: Dimethyl sulfoxide; SR-BI: scavenger receptor class B type I; ER: Endoplasmic reticulum; PHH: Primary human hepatocytes; PTH: Primary Tupaia belangeri hepatocytes; DMSO: Dimethylsulfoxide.