Elucidation of the effect of HCV propagationa and IFN sensitivity by amino acid substitution in interferon sensitivity-determining region.

2017 Fiscal Year Final Research Report

• Project/Area Number: 26860309
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases (2014, 2016-2017); Yokohama City University (2015)
• Principal Investigator: SUGIYAMA Ryuichi 国立感染症研究所, ウイルス第二部, 研究員 (70714476)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: C型肝炎ウイルス / NS5A / インターフェロン / 薬剤感受性

Outline of Final Research Achievements

To assess the involvement of ISDR in the HCV life cycle and to clarify the molecular mechanisms influencing IFN susceptibility, we used recombinant JFH-1 viruses with NS5A of the genotype 1b Con1 strain (JFH1/5ACon1) and with NS5A ISDR containing 7 amino acid substitutions (JFH1/5ACon1/i-7mut), and compared the virus propagation and the induction of ISGs. By transfecting RNAs of these strains into cells, we found that the efficiency of infectious virus production of JFH1/5ACon1/i-7mut was attenuated compared with JFH1/5ACon1. After transfecting RNA into cells, the mRNA expression of ISGs was sufficiently induced by IFN treatment in JFH1/5ACon1/i-7mut-transfected but not in JFH1/5ACon1-transfected cells. These data suggested that the NS5A-mediated inhibition of ISG induction was deteriorated by amino acid substitutions in the ISDR. These observations explain the strain-specific evasion of IFN signaling by HCV.

Free Research Field

ウイルス学