2011 Fiscal Year Final Research Report
Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91.
| Project/Area Number |
22790633
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
NAKAGAWA Mina 東京医科歯科大学, 医学部附属病院, 助教 (30401342)
|
|---|
| Project Period (FY) |
2010 – 2011
|
| Keywords | IFN治療抵抗性 / HCVコア変異株 / インターロイキン(IL)-6 / 小胞体(ER)ストレス |
|---|
| Research Abstract |
Here we investigated mechanisms of difference in the response to alpha interferon(IFN) by using HCV cell culture with HCV core mutant R70Q, R70H, and L91M virus clones The expression level of an interferon signal attenuator, SOCS3, was significantly higher for the R70Q, R70H, and L91M mutants than for the wild type. Interleukin 6(IL-6), which upregulates SOCS3, was significantly higher for the R70Q, R70H, and L91M mutants than for the wild type, suggesting interferon resistance, possibly through IL-6-induced, SOCS3-mediated suppression of interferon signaling. Expression levels of endoplasmic reticulum(ER) stress proteins were significantly higher in cells transfected with a core mutant than in those transfected with the wild type. The HCV-2b/JFH1chimeric virus, which was constructed in our laboratory, able to infect Huh7. 5. 1 cells and was significantly more sensitive to IFN than JFH1. The IFN resistance of JFH1 cells was negated by siRNA-knock down of SOCS3 expression and by pretreatment with anti-IL6 antibody. These data suggest that these differences of IFN sensitivity of HCV may be attributable to the sequences of HCV structural proteins and can be determined by SOCS3 and IL-6 expression levels, which might be induced by ER etress.
|
Research Products
(34 results)
