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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 97 - 106 (10page)
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초록· 키워드
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Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. HCV core protein plays not only a structural role in the virion morphogenesis by encapsidating a virus RNA genome but also a non-structural role in HCV-induced pathogenesis by blocking innate immunity. Especially, it has been shown to regulate JAK-STAT signaling pathway through its direct interaction with Janus kinase (JAK) via its proline-rich JAK-binding motif ($^{79}{\underline{P}}GY{\underline{P}}WP^{84}$). However, little is known about the physiological significance of this HCV core-JAK association in the context of the virus life cycle. In order to gain an insight, a mutant HCV genome (J6/JFH1-79A82A) was constructed to express the mutant core with a defective JAK-binding motif ($^{79}{\underline{A}}GY{\underline{A}}WP^{84}$) using an HCV genotype 2a infectious clone (J6/JFH1). When this mutant HCV genome was introduced into hepatocarcinoma cells, it was found to be severely impaired in its ability to produce infectious viruses in spite of its robust RNA genome replication. Taken together, all these results suggest an essential requirement of HCV core-JAK protein interaction for efficient production of infectious viruses and the potential of using core-JAK blockers as a new anti-HCV therapy.
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참고문헌 (41)
참고문헌 신청
Aaronson, D. S. / 2002 / A road map for those who don't know JAK-STAT / Science 296:1653~1655
Alter, M. J. / 1994 / The prevalence of hepatitis C virus infection in the United States, 1988 through 1994 / N. Engl. J. Med 341:556~562
Bach, E. A. / 1997 / The IFN gamma receptor: a paradigm for cytokine receptor signaling / Annu. Rev. Immunol 15:563~591
Barba, G. / 1997 / Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets / Proc. Natl Acad. Sci. U.S.A 94:1200~1205
Basu, A. / 2001 / Hepatitis C virus core protein modulates the interferon-induced transacting factors of Jak/Stat signaling pathway but does not affect the activation of downstream IRF-1 or 561 gene / Virology 288:379~390
Alter, M. J. / 1994 / The prevalence of hepatitis C virus infection in the United States, 1988 through 1994 / N. Engl. J. Med 341:556~562
Bach, E. A. / 1997 / The IFN gamma receptor: a paradigm for cytokine receptor signaling / Annu. Rev. Immunol 15:563~591
Barba, G. / 1997 / Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets / Proc. Natl Acad. Sci. U.S.A 94:1200~1205
Basu, A. / 2001 / Hepatitis C virus core protein modulates the interferon-induced transacting factors of Jak/Stat signaling pathway but does not affect the activation of downstream IRF-1 or 561 gene / Virology 288:379~390
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