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 *help |
¥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.
|
Report
(4 results)
Research Products
(4 results)
