gt(rosa)26sor , b6;129-gt(rosa)26sor / j and b6;129s2-scarb1/j and fvb / nj wild - type mice were obtained from the jackson laboratory ( bar harbor , me ) .
mice were bred and maintained at the comparative bioscience center of the rockefeller university according to guidelines established by the institutional animal committee .
adenoviral constructs encoding human and murine homologues of the four hcv entry factors ( cd81 , scarb1 , cldn1 and ocln ) and mutants thereof were created using the adeasy adenoviral vector system ( agilent technologies , santa clara , ca ) according to the manufacturer s instructions .
plasmids encoding chimeric hcv genomes , including jc1flag2(p7fluc2a ) and bicistronic hcv genomes expressing cre , were linearized with xbai and transcribed using megascript t7 ( ambion , austin , texas ) .
rna was electroporated into huh-7.5 cells using a ecm 830 electroporator ( btx genetronics ) and infectious virus was collected from supernatants 4872 h after transfection .
gt(rosa)26sor , b6;129-gt(rosa)26sor / j and b6;129s2-scarb1/j and fvb / nj wild - type mice were obtained from the jackson laboratory ( bar harbor , me ) .
mice were bred and maintained at the comparative bioscience center of the rockefeller university according to guidelines established by the institutional animal committee .
adenoviral constructs encoding human and murine homologues of the four hcv entry factors ( cd81 , scarb1 , cldn1 and ocln ) and mutants thereof were created using the adeasy adenoviral vector system ( agilent technologies , santa clara , ca ) according to the manufacturer s instructions .
plasmids encoding chimeric hcv genomes , including jc1flag2(p7fluc2a ) and bicistronic hcv genomes expressing cre , were linearized with xbai and transcribed using megascript t7 ( ambion , austin , texas ) .
rna was electroporated into huh-7.5 cells using a ecm 830 electroporator ( btx genetronics ) and infectious virus was collected from supernatants 4872 h after transfection .
 hepatitis c virus ( hcv ) remains a major medical problem . 
 antiviral treatment is only partially effective and a vaccine does not exist . 
 development of more effective therapies has been hampered by the lack of a suitable small animal model . 
 while xenotransplantation of immunodeficient mice with human hepatocytes has shown promise , these models are subject to important challenges . 
 building on the previous observation that cd81 and occludin ( ocln ) comprise the minimal human factors required to render mouse cells permissive to hcv entry in vitro , we attempted murine humanization via a genetic approach . here 
 we show that expression of two human genes is sufficient to allow hcv infection of fully immunocompetent inbred mice . 
 we establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scarb1 for hcv uptake . 
 we demonstrate that hcv can be blocked by passive immunization , as well as show that a recombinant vaccinia virus ( rvv ) vector induces humoral immunity and confers partial protection against heterologous challenge . 
 this system recapitulates a portion of the hcv life cycle in an immunocompetent rodent for the first time , opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing hcv entry inhibitors in vivo . 
Methods summary
Mice
Recombinant adenoviruses
Hepatitis C virus
Supplementary Material