Involvement of the 3' Untranslated Region in Encapsidation of the Hepatitis C Virus

PLoS Pathog. 2016 Feb 11;12(2):e1005441. doi: 10.1371/journal.ppat.1005441. eCollection 2016 Feb.


Although information regarding morphogenesis of the hepatitis C virus (HCV) is accumulating, the mechanism(s) by which the HCV genome encapsidated remains unknown. In the present study, in cell cultures producing HCV, the molecular ratios of 3' end- to 5' end-regions of the viral RNA population in the culture medium were markedly higher than those in the cells, and the ratio was highest in the virion-rich fraction. The interaction of the 3' untranslated region (UTR) with Core in vitro was stronger than that of the interaction of other stable RNA structure elements across the HCV genome. A foreign gene flanked by the 3' UTR was encapsidated by supplying both viral NS3-NS5B proteins and Core-NS2 in trans. Mutations within the conserved stem-loops of the 3' UTR were observed to dramatically diminish packaging efficiency, suggesting that the conserved apical motifs of the 3´ X region are important for HCV genome packaging. This study provides evidence of selective packaging of the HCV genome into viral particles and identified that the 3' UTR acts as a cis-acting element for encapsidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / physiology*
  • 5' Untranslated Regions / genetics
  • Cell Line
  • Hepacivirus / genetics*
  • Humans
  • RNA, Viral / genetics*
  • Viral Nonstructural Proteins / metabolism
  • Virion / metabolism
  • Virus Assembly / genetics*


  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • RNA, Viral
  • Viral Nonstructural Proteins

Grant support

This work was supported in part by grants-in-aid from the Ministry of Health, Labor, and Welfare of Japan and from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and by Research on Health Sciences Focusing on Drug Innovation from the Japan Health Sciences Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.