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

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

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Department of Infectious Diseases, Hamamatsu University School of Medicine, Shizuoka, Japan.
Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Research and Education center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Research Institute of Biosciences, Azabu University, Kanagawa, Japan.
Proteo-Science Center, Ehime University, Ehime, Japan.


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.

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