Amino Acid Polymorphism in HCHV Core Affects Infectious Virus Production and MHC Class I Molecule Expression

• Project/Area Number: 24591000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KATO Takanobu 国立感染症研究所, ウイルス第二部, 室長 (20333370)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HCV / インターフェロン / 薬剤耐性 / 慢性肝炎 / C型肝炎ウイルス / 薬剤感受性 / 肝発癌

Outline of Final Research Achievements

Amino acid polymorphisms in the HCV genotype 1b core protein has been reported to be a potent predictor for poor response to IFN-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of R/Q at aa 70 and L/M at aa 91. We found that the polymorphism at aa 70 was associated with efficiency of infectious virus production, and this deteriorated virus production in strains with aa70Q resulted in the intracellular accumulation of HCV proteins and attenuation of MHC class I molecule expression induced by IFN treatment through enhanced protein kinase R phosphorylation. These observations may explain the strain-associated resistance to IFN-based therapy and hepatocarcinogenesis of HCV.

Research Products

• [Presentation] HCV Core領域アミノ酸70/91変異株を用いた反応機序の解析 (2013)
  • Author(s): 藤田めぐみ，加藤孝宣，村山麻子，山田典栄，朝比奈靖浩，坂本直哉
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] Substitution of amino acid 70/91 in the hepatitis C core region affects infectious virus production and cell surface expression of MHC Class I. (2013)
  • Author(s): Megumi Tasaka-Fujita, Nao-Sugiyama, Wonseok Kang, Asako Murayama, Naoya Sakamoto, Takaji Wakita, Eui-cheoul Shin, Takanobu Kato.
  • Organizer: The 64th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Washington DC
• [Presentation] HCV core領域アミノ酸70/91変異株を用いた反応機序の解析 (2013)
  • Author(s): 藤田めぐみ、加藤孝宣、村山麻子、山田典枝、脇田隆字、朝比奈靖浩、坂本直哉
  • Organizer: 第４９回日本肝臓学会総会
  • Place of Presentation: 京王プラザホテル
• [Presentation] HCV genotype 1b株キメラウイルスを用いたHCV core領域アミノ酸70/91変異株の解析 (2012)
  • Author(s): 藤田めぐみ、脇田隆字、加藤孝宣
  • Organizer: 第４８回日本肝臓学会総会
  • Place of Presentation: ホテル日航金沢