Figure 1.

HCV genome structure. (top) Organization of the positive-sense RNA genome of HCV. 5′ and 3′ UTRs contain cis-acting elements required for viral protein expression and RNA synthesis, including an internal ribosome entry site (IRES) in the 5′UTR that directs cap-independent translation of the viral polyprotein. The polyprotein (large box) is processed by both host and virus-encoded proteases to produce the individual proteins required for viral genome replication, virus assembly, and production of infectious progeny virus (reviewed in Moradpour et al 2007). The structural proteins (blue) that form the HCV virion include core (nucleocapsid), E1 and E2 (envelope glycoproteins). Non-structural proteins of HCV serve a variety of functions including RNA genome replication, virus assembly and maturation: those from NS3-NS5B (pink) are required for genome replication. NS3 has distinct proteinase and helicase domains, while NS4A is cofactor that intercalates with NS3 and is required for full expression of NS3 protease activity. NS4B is involved in the formation of the membranous web: a cytoplasmic structure associated with the viral RNA replicase. NS5A is an essential co-factor for virus replication and assembly, while NS5B is the viral RNA-dependent RNA polymerase. p7 and NS2 (green) are additional nonstructural proteins that are not required for viral RNA synthesis but contribute to virion assembly and egress. (bottom) Organization of a dicistronic, selectable HCV “replicon”. The 5′ and 3′UTRs are as in the viral genome. A truncated core-protein sequence is fused to the neomycin phosphotransferase gene, followed downstream by a heterologous picornaviral IRES driving translation of the nonstructural proteins. This RNA is capable of autonomous amplification in permissive cells, but does not generate infectious virus.