Identification of cis-acting element for packaging of hepatitis C virus genome

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390111
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUZUKI Tetsuro 浜松医科大学, 医学部, 教授 (00250184)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Ryosuke 国立感染症研究所, ウイルス第二部, 主任研究官 (50342902) ; ITO Masahiko 浜松医科大学, 医学部感染症学講座, 助教 (50385423)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ウイルス / ゲノムパッケージング / 粒子形成 / C型肝炎ウイルス

Outline of Final Research Achievements

The mechanism(s) by which the hepatitis C virus (HCV) genome becomes encapsidated remains unknown. Deep sequencing demonstrated that a majority of particle-associated HCV RNAs are genome-sized. In cell cultures producing HCV, molecular ratios of 3’ end viral RNA to 5’ end positively correlated with infectivity of fractions and that of virion-rich fraction was the highest, suggesting selective encapsidation of genome RNA. Using trans-complementation systems, the 3’ untranslated region (UTR) of the genome was identified as a cis-acting element for RNA packaging. Mutations within the stem-loops at the 3’ end of the 3’ UTR were observed to diminish packaging efficiency. A foreign gene flanked by the 3’ UTR was encapsidated by supplying both viral NS3-NS5B proteins and Core-NS2 in trans. This study provides the first direct evidence of selective packaging of the HCV genome into the viral particles potentially through 3’ UTR-Core binding.

Free Research Field

ウイルス学