丙型肝炎病毒核心蛋白对干扰素诱导的抗病毒基因表达的影响及其机制.pdfVIP

VIROLOGICA SINICA, October 2007, 22 (5):374-379 CLC number: R512.6 Document code: A Article ID: 1674-0769(2007)05-0374-06 Effect of Hepatitis C Virus Core Protein on Interferon-Induced Antiviral Genes Expression and Its Mechanisms 1 2 1 1 1 Yan-zi CHANG , Yan-chang LEI , Wen WU , Shan-shan CHEN , Han-ju HUANG , 2 1** Dong-liang YANG and Meng-ji LU (1. Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; 2. Division of Clinical Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.) Abstract: Emerging data indicated that HCV subverts the antiviral activity of interferon (IFN); however, whether HCV core protein contributes to the process remains controversial. In the present study, we examined the effect of HCV core protein on interferon-induced antiviral gene expression and whether the effect is involved in the activation and negative regulation of the Jak/STAT signaling pathway. Our results showed that, following treatment with IFN-α，the transcription of PKR, MxA and 2’-5’OAS were down-regulated in HepG2 cells expressing the core protein. In the presence of HCV core protein, ISRE-dependent luciferase activity also decreased. Further study indicated that the core protein could inhibit the tyrosine phosphorylation of STAT1, whereas the level of STAT1 expression was unchanged. Accordingly, SOCS3, the negative regulator of the Jak/STAT pathway, was induced by HCV core protein. These results