Volume 44, Issue 2, Pages 411-421 (February 2006) The face of future hepatitis C antiviral drug development: Recent biological and virologic advances and their translation to drug development and clinical practice  John G. McHutchison, Ralf Bartenschlager, Keyur Patel, Jean-Michel Pawlotsky  Journal of Hepatology  Volume 44, Issue 2, Pages 411-421 (February 2006) DOI: 10.1016/j.jhep.2005.12.001 Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Cell-based assays for the study of hepatitis C virus (HCV) replication in cell culture. (A) Structure of a subgenomic HCV replicon carrying a selectable marker (neo) that confers G418-resistance. Translation of neo is mediated by the HCV IRES, whereas NS3 to NS5B are translated under control of the encephalomyocarditis virus IRES. (B) Schematic of the structure of an HCVpp. It is composed of the envelope into which E1–E2 glycoprotein complexes are embedded, the HIV nucleocapsid (CA), and two copies of an HIV vector RNA carrying a reporter gene such as green fluorescent protein. (C) Generation of infectious HCV in cell culture. Huh-7 cells are transfected with genomic HCV RNA depicted in the top (the authentic JFH-1 genome or a JFH1-chimera in which the region from core up to the N-terminus of NS2 [indicated by shading] stems from another HCV isolate). Four days later, culture supernatant is harvested, used to inoculate naive Huh-7 cells, and after 2 further days cells are analyzed for infection by using a NS3-specific immunofluorescence assay (lower panel). Infection was performed directly with supernatant (left panel) or with supernatant containing either a CD81-specific antibody or a control antibody (right and middle panel, respectively). Note the strong reduction of the number of infected cells when infections are performed in the presence of the CD81-specific antibody. Journal of Hepatology 2006 44, 411-421DOI: (10.1016/j.jhep.2005.12.001) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions