초록 ▼

1. C형 간염바이러스에 감염된 환자의 혈청 및 간암조직을 이용하여 인터페론 내성과 관련이 있는 genotype 1b와 2a의 유전자의 sequence 비교, 분석 및 cloning.
2. Genotype 1b와 2a의 cloning한 유전자를 이용한 stable cell line 제조.
3. Microarray를 통한 각각의 genotype에서 특이적으로 조절되는 유전자를 확보.
4. C형 간염바이러스의 각각의 genotype에 따른 단백질 상호 작용의 변화 분석.
5. C형 간염바이러스의 genotype의

1. C형 간염바이러스에 감염된 환자의 혈청 및 간암조직을 이용하여 인터페론 내성과 관련이 있는 genotype 1b와 2a의 유전자의 sequence 비교, 분석 및 cloning.
2. Genotype 1b와 2a의 cloning한 유전자를 이용한 stable cell line 제조.
3. Microarray를 통한 각각의 genotype에서 특이적으로 조절되는 유전자를 확보.
4. C형 간염바이러스의 각각의 genotype에 따른 단백질 상호 작용의 변화 분석.
5. C형 간염바이러스의 genotype의 차이에 의한 interferon response의 차이를 분석.

Abstract ▼

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Currently, neither vaccine nor an effective chemotherapy is available for HCV infection. Interferon (IFN) is the only available treatment for HCV patients. However, IFN is not effective for

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Currently, neither vaccine nor an effective chemotherapy is available for HCV infection. Interferon (IFN) is the only available treatment for HCV patients. However, IFN is not effective for a majority of HCV patients. It is because viruses often counteract with elaborate strategies to interfere with the action of IFN and its effector molecules. For unknown reasons, sustained virologic response (SVR) for HCV genotype 1b is much lower than genotype 2a. Since genotype 1b is one of the major HCV genotypes in Korea, it is necessary to analyze the molecular mechanisms of different SVR among genotypes.
Our final goal is to develop effective therapeutic agents to cure HCV patients based on current data. In this study, we investigated the molecular mechanisms underlying different SVR among genotypes using serum and HCC liver samples isolated from HCV patients, We compared sequence variance between genotype 1b and 2a. Using stable cell lines expressing either genotype 1b or 2a, we isolated cellular genes regulated differently between genotypes. We found that both NS3 and NS5A proteins were involved in regulation of IFN gene expression. Importantly, NS5A protein of genotype 1b inhibited IFN-$\alpha$, IFN-$\beta$, and IFN gene expression more than NS5A of genotype 2a. We further found that IFN production was blocked by interaction with $IKK{\varepsilon}$ and by inhibiting phosphorylation of STAT1a protein. In addition, we found that interferon regulatory factor 3 (IRF3) was mostly modulated by HCV genotype 1b NS5A compared to genotype 2a NS5A. These data suggest that NS5A protein plays a major role in IFN-mediated antiviral response and hence highlights the importance of therapeutic strategy for IFN nonresponders among HCV patients.

목차 Contents

• 표지...1
• 제출문...2
• 목차...3
• I. 총괄현황...4
• 보고서 요약서...5
• 요약문...6
• SUMMARY...8
• 연구 성과 실적 및 향후 계획...9
• 참여연구원 현황표...13
• II. 총괄연구과제 연구결과...14
• 1. 연구개발과제의 배경 및 필요성...15
• 2. 국내외 기술개발 현황...22
• 3. 연구개발과제의 추진체계...24
• 4. 연구개발수행 내용 및 결과...26
• 5. 목표달성도 및 관련분야 기여도...63
• 6. 향후 연구성과 추진 계획...66
• 7. 연구개발결과의 파급효과...67
• 8. 연구개발결과의 활용계획...68
• 9. 연구개발과정에서 수집한 해외과학기술정보...68
• 10. 참고문헌...69
• III. 제 O 세부연구과제 연구결과...72
• 1. 연구개발과제의 목표...73
• 2. 연구개발과제의 추진 체계...73
• 3. 연구개발과제의 내용 및 결과...73
• 4. 참고문헌...73
• IV. 첨부서류...74
• 1. 자체평가의견서...76
• 2. 실적 증빙자료...81
• 3. 기타 첨부양식...81