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Copyright ©2007 Baishideng Publishing Group Co.
World J Gastroenterol. May 7, 2007; 13(17): 2427-2435
Published online May 7, 2007. doi: 10.3748/wjg.v13.i17.2427
Table 1 HCV infection trials in animals
VirusAnimal testedInfectionOriginal reference
HCVNon human primatesChimpanzeeYesAlter et al[2] 1978
MarmosetYesFeinstone et al[71] 1981
Cottontop tamarinNoGarson et al[72] 1997
Cynomoglus monkeyNo
Rhesus monkeyNo
Green monkeyNo
Japanese monkeyNoAbe et al[73] 1993
Doguera baboonNo
Chacma baboonNoSithebe et al[74] 2002
ScandentiaTupaiaYesXie et al[75] 1998
RodentsuPA/SCID miceYesMercer et al[26] 2001
Trimera miceYesGalun et al[10] 1995
RatYesWu et al[8] 2005
WoodchuckNoAbe et al[73] 1993
Table 2 Characteristics of HCV infection in three rodent models
Rodent modelsHumanizationViremiaDuration of viral infectionCommentsPublications
uPA/SCID miceHuman hepatocyte transplantation1 × 104 to 8 × 107 copies/mLUp to 9 mo with maximum viremia as from one monthHigh viremia
Variability of primary human hepatocytesMercer et al[26] 2001
Meuleman et al[22] 2005
Immunosuppressed miceKneteman et al[29] 2006
Trimera miceXenograft of human liver tissueAround 7 × 104 copies/mLAround one month with peak viremia at 18 dLow viremia
Variability of human liver tissuesIlan et al[12] 2002
Immunosuppressed miceEren et al[11] 2006
RatImmunotolerization and transplantation of a human hepatoma cell line1-2 × 104 copies/mLMinimum 4 mo with peak viremia at 3 moLow viremia
Transplantation of a hepatoma cell lineWu et al[8] 2005
Immunocompetent rat
Table 3 Transgenic mice expressing HCV proteins
Viral proteinOriginal reference of the transgenic mouseMouse strainPromoterCommentsReferences
CoreMoriya et al[42] 1997C57BL/6HBVSteatosisMoriya et al[40] 1998
HCCMoriya et al[42] 1997
Oxidative stressMoriya et al[41] 2001
Increased concentration of monounsaturated fatty acidsMoriya et al[37] 2001
Inhibition of microsomal triglyceride transfer protein activity and VLDL secretion.Perlemuter et al[38] 2002
Alcohol and core protein increase lipid peroxidationPerlemuter et al[39] 2003
Alteration of intrahepatic cytokine expression and AP-1 activationTsutsumi et al[45] 2002
Interaction with retinoid X receptor alphaTsutsumi et al[43] 2002
Cooperation with ethanol activation of MAPKTsutsumi et al[44] 2003
Insulin resistanceShintani et al[34] 2004
Koike et al[33] 2006
Modulation of interferon pathway (Inhibition of SOCS-1 expression)Miyoshi et al[47] 2005
ER stress, apoptosisBenali-Furet et al[78] 2005
CoreHonda et al[52] 2000C57BL/6HBVModulated sensitivity to Fas-mediated apoptosisHonda et al[52] 2000
Insulin resistance via down-regulation hepatic IRS1 and 2Kawaguchi et al[35] 2004
Constitutive activation of STAT3, implication in HCCYoshida et al[46] 2002
CorePasquinelli et al[50] 1997C57BL/6Major urinary proteinNo liver diseasePasquinelli et al[50] 1997
Core (Korean wt and mutants)Wang et al[79] 2004C57BL/6JHBVCell dysplasia for S99Q core mutantWang et al[79] 2004
Core (in T cell)Soguero et al[53] 2002C57BL/6CD2Increased Fas-mediated apoptosis and liver infiltration of peripheral T cellsSoguero et al[53] 2002
Double Tg core X TCRCruise et al[55] 2005C57BL/6 × DO11.10 (H-2d)Increased Fas ligand expression of CD4+ T cells associated with liver inflammationCruise et al[55] 2005
Role of CXCR3 ligands via Fas induction, during the inflammatory responseCruise et al[54] 2006
CoreIshikawa et al[48] 2003C57BL/6Nserum amyloidMalignant lymphoma and Hepatocellular adenoma in old miceIshikawa et al[48] 2003
CoreKato et al[49] 2003C57BL/6serum amyloid PAdenoma and HCC development in transgenic mice following repeated CCl4 administrations.Kato et al[49] 2003
Core Core-E1-E2Kamegaya et al[51] 2005FVB × C57BL/6AlbuminAfter DEN treatment, core-E1-E2 mice develop tumors with a larger size than core mice (diminution of apoptotic index)Kamegaya et al[51] 2005
Core-E1-E2-p7Lerat et al[62] 2002C57BL/6AlbuminSteatosisLerat et al[62] 2002
HCC (rare)
Sensitivity to oxidative stressOkuda et al[80] 2002
Core-E1-E2-p7Korenaga et al[81] 2005C57BL/6JAlbuminIncrease in ROS production by mitochondrial electron transport complex IKorenaga et al[81] 2005
Core-E1-E2Kawamura et al[82] 1997FVBAlbumin or major urinary proteinNo liver diseaseKawamura et al[82] 1997
Core-E1-E2Honda et al[56] 1999C57BL/6H2-KdSensitivity to anti-fas administrationHonda et al[56] 1999
Core-E1-E2Naas et al[57] 2005C57BL/6CMVSteatosis.Naas et al[57] 2005
Acceleration of liver and lymphoid tumor development
Core-E1-E2-NS2Wakita et al[59] 1998Balb/CCre/Lox system (CAG promoter)Hepatitis injury associated with HCV-specific CTL responseWakita et al[59] 1998 Wakita et al[58] 2000
Suppression of Fas-mediated cell deathMachida et al[83] 2001
HCV-specific CD8+ CTLs specifically induce liver injuryTakaku et al[62] 2003
E1-E2Koike et al[63] 1995CD1HBVNo liver diseaseKoike et al[63] 1995
Expression in salivary glands
Exocrinopathy resembling Sjogren syndromeKoike et al[84] 1997
E2Pasquinelli et al[50] 1997C57BL/6AlbuminNo liver diseasePasquinelli et al[50] 1997
NS3-NS4AFrelin et al[64] 2006C57BL/6Major urinary proteinNo liver disease.Frelin et al[64] 2006
Alteration of hepatic immune cell subsets.
Reduced sensitivity to TNF alpha mediated liver disease.
NS5Majumder et al[65] 2002FVBApoENo liver diseaseMajumder et al[65] 2002
Protection against TNF alpha mediated liver disease (inhibition of NF-kappaB activation)Majumder et al[66] 2003
Full polyproteinAlonzi et al[60] 2004C57BL/6Alpha1 antitrypsinSteatosisAlonzi et al[60] 2004
Blindenbacher et al[67] 2003T cell infiltrate
Inhibition of IFN alpha-induced signalingBlindenbacher et al[67] 2003
Increased expression of protein phosphatase 2ADuong et al[68] 2004
Full polyproteinLerat et al[62] 2002C57BL/6AlbuminHepatic steatosis, HCCLerat et al[62] 2002
Impairment of intrahepatic immune response (absence of elimination of adenovirus-infected hepatocytes)Disson et al[85] 2004
Down-regulation of pro-apoptotic CIDE-B protein in adenovirus-infected transgenic miceErdtmann et al[86] 2003
Iron overload induces increase the risk of HCC (mitochondrial injury)Furutani et al[87] 2006