Molecular Basis of Encapsidation of Hepatitis C Virus Genome

Abstract

Hepatitis C virus (HCV), a major etiologic agent of human liver diseases, is a positive-sense single-stranded RNA virus and is classified in the Flaviviridae family. Although research findings for the assembly of HCV particles are accumulating due to development of HCV cell culture system, the mechanism(s) by which the HCV genome becomes encapsidated remains largely unclear. In general, viral RNA represents only a small fraction of the RNA molecules in the cells infected with RNA viruses, but the viral genomic RNA is considered to selectively packaged into virions. It was recently demonstrated that HCV RNAs containing 3' end of the genome are selectively incorporated into virus particles during the assembly process and the 3' untranslated region functions as a cis-acting element for RNA packaging. Here, we discuss the molecular basis of RNA encapsidation of HCV and classical flaviviruses, contrast with the packaging mechanism of HIV-1.

Keywords: cis-acting element; encapsidation; hepatitis C virus; packaging signal; virion assembly.

FIGURE 1

Depicted secondary structures of 5′- and 3′ UTRs of HCV genome. The 5′ UTR contains four structured domains (I–IV). The translational start codon is indicated. Two types of conformations for the 3′X region (shadowed region) within the 3′ UTR have been proposed.

FIGURE 2

Proposed model for encapsidation of HCV genome. Newly synthesized HCV genomic RNA is released from membrane vesicles containing the replication complex (lower left). It may be likely that the viral genome bound to NS5A is recruited to the surface of lipid droplets, enabling its interaction with Core. For nucleocapsid formation, the 3′ UTR of the HCV genome acts as a cis-acting element for RNA packaging. Within the 3′ UTR region, the loop sequences of stem-loop structures appear to be essential for HCV encapsidation.