Proapoptotic and pronecrosis effect of different truncated hepatitis C virus core proteins

• Published in: Journal of Zhejiang University. B. Science 2005-04, Vol.6 (4), p.295-300
• Main Author: 陈智 骆东辉 许晓燕 吴炜 周林福
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomedicine; Cell Line, Tumor; HCV; Hepacivirus - genetics; Hepacivirus - pathogenicity; Hepacivirus - physiology; Humans; Necrosis - virology; Sequence Deletion - genetics; Viral Core Proteins - chemistry; Viral Core Proteins - genetics; Viral Core Proteins - metabolism; 丙型肝炎病毒; 核蛋白; 细胞坏死; 脱噬作用
• ISSN: 1673-1581; 1009-3095; 1862-1783
• DOI: 10.1631/jzus.2005.b0295

Objective: To study the roles of different truncated hepatitis C virus (HCV) core proteins (CORE) in the pathogenesis of HCV persistent infection and hepatocellular carcinoma (HCC) and to assess intracellular localization in transiently transfected cells. Methods: Seven truncated CORE-GFP (green fluorescent protein) fusion protein expression plasmids were constructed, which contained HCV CORE sequences derived from tumor tissues (BT) and non-tumor tissues (BNT) from one patient infected with HCV. Amino acid (aa) lengths were BT: 1-172 aa, 1-126 aa, 1-58 aa, 59-126 aa, 127-172 aa; BNT: 1-172 aa and C191: 1-172 aa respectively. Subcellular localization of CORE-GFP was analyzed by con-focal laser scanning microscope. Apoptosis and necrosis were quantified by flow cytometry. Results: Different truncated CORE-GFP localized mainly in the cytoplasm, but nuclear staining was also observed. HCV CORE could induce apoptosis and necrosis, and different truncated COREs could induce cell apoptosis and necrosis at different levels. Among the same length 1-172 aa of BT, BNT and C191, the cell apoptosis and necrosis percentage of BT is highest, and Cl91 is the lowest (BT>BNT>C191). To the different fragment COREs of BT, N-terminal of CORE induced apoptosis and necrosis higher, compared with that of C-terminal (1-172 aa>1-126 aa>1-58 aa> 127-172 aa>59-126 aa). Conclusion: These results suggest HCV CORE could induce apoptosis and necrosis of cells, which might play an important role in the pathogenesis of HCV persistent infection and HCC and the different CORE domains of different HCV quasi-species might have some difference in their pathogenesis.