https://scholars.lib.ntu.edu.tw/handle/123456789/568619
標題: | The non-structural 5A protein of hepatitis C virus exhibits genotypic differences in interferon antagonism | 作者: | Tsai Y.-H. Kuang W.-F. Lu T.-Y. JIA-HORNG KAO Lai M.-Y. CHUN-JEN LIU PEI-JER CHEN Hwang L.-H. |
公開日期: | 2008 | 出版社: | Elsevier | 卷: | 49 | 期: | 6 | 起(迄)頁: | 899-907 | 來源出版物: | Journal of Hepatology | 摘要: | Background/Aims: Patients infected with hepatitis C virus (HCV) genotype 2 or 3 usually respond better to interferon (IFN) treatment than those infected with genotype 1. In this study, we investigated whether the non-structural 5A protein (NS5A) of HCV genotypes 1 and 2 (1b-NS5A and 2a-NS5A, respectively) exerted differential counteractivities against IFN treatment. Methods: We compared the inhibitory effects of 1b-NS5As and 2a-NS5As on IFN activity. We also investigated the replication inhibition of HCV subgenomic replicons containing 1b-NS5A or 2a-NS5A in response to IFN treatment. Results: 1b-NS5As exerted more profound inhibitory effects on IFN activity than 2a-NS5As. The replication of the 2a-NS5A-containing replicons was more sensitive to IFN treatment than that of the 1b-NS5A-containing replicons. Deletion of the interferon sensitivity-determining region/protein kinase R-binding domain (PKR-BD), the V3 domain, or the C-terminus region of NS5A significantly abrogated its anti-IFN activity. Domain swapping between 1b-NS5A and 2a-NS5A in the V3 domain and/or the C-terminus region resulted in a transfer of their anti-IFN activity. Conclusions: 1b-NS5As exert higher magnitudes of IFN antagonism than do 2a-NS5As. The V3 and the C-terminus regions are responsible for the differential anti-IFN effects. This phenomenon may partly explain the genotype-linked differences in the response of HCV to IFN treatment. ? 2008 European Association for the Study of the Liver. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984559137&doi=10.1016%2fj.jhep.2008.06.030&partnerID=40&md5=ac33638d2b1a4774df8b6a3024c0b2f3 https://scholars.lib.ntu.edu.tw/handle/123456789/568619 |
ISSN: | 0168-8278 | DOI: | 10.1016/j.jhep.2008.06.030 | SDG/關鍵字: | interferon; nonstructural protein 5A; vasopressin V3 receptor; article; carboxy terminal sequence; cell line; culture medium; drug activity; drug sensitivity; genetic resistance; genotype; HeLa cell; Hepatitis C virus; human; human cell; polymerase chain reaction; priority journal; treatment response; Vero cell; virus replication |
顯示於: | 臨床醫學研究所 |
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