Cell culture and mouse model Control Huh7 cells and Huh7 cells with genome-length replicon, subgenomic replicon, or the tet-inducible core expression construct were used for this study. All three HCV proteinexpressing cell lines have been described previously [20, 26] . Genome-length replicon and subgenomic replicon were derived from a genotype 1a H77c infectious molecular clone [20] . The genome-length replicon encodes the full-length HCV polyprotein (core, E1, E2, p7, and NS2-NS5), whereas the subgenomic replicon encodes only the non-structural proteins NS2-NS5B [20] . The tet-inducible core-expressing cells express core protein in the absence of doxycycline. These cells are referred to as Core-on cells when core expression is turned on and as Core-off cells when core expression is turned off by the addition of doxycycline to the culture medium. All cells were maintained in DMEM with 10% tetracycline-free fetal calf serum (FCS, Clontech, Mountain View, CA, USA), Pen/Strep (50 IU/ml penicillin and 50 mg/ml streptomycin), and G418 (200 mg/ml) plus the following antibiotics: genome-length and subgenomic replicon cells, 5 mg/ml blasticidin; Core-off cells, 20 mg/ml doxycycline. When cells were plated for an experiment, only DMEM with 10% tetracycline-free FCS and Pen/Strep was used. All cells were incubated at 37uC with 5% CO 2 . Expression of HCV proteins in genome-length and subgenomic replicon cells were monitored by following the specific activities of the reporter gene, secreted alkaline phosphatase (SEAP), in the culture medium at 48 to 72 hrs after the initial plating [51] ; HCV core protein expression in genome-length replicon and Core-on cells were monitored by western blot analysis.