建立一個真實的C型肝炎病毒感染及複製系統

C型肝炎病毒（HCV）為黃熱病毒科之病毒，被證實為非A非B型肝炎的致病源，大多經由血液所感染的，感染後通常會造成慢性肝炎、肝硬化等不同嚴重程度的肝臟疾病，與肝癌的發生有密切的關係。先前，我們曾證實了一肝臟因子（Sip-L）可以支持C型肝炎病毒在一非感染性的細胞株293 EBNA cells中複製。不同物種中皆可發現有與此肝臟因子胺基酸序列類似的蛋白，這其中包括Oryza Sativa submergence-induced protein 2A，因此命名為Sip-L。在HCV感染此細胞株後可使得HCV-RNA迅速複製並分泌出來以感染新的細胞。我們利用293EBNA表現Sip-L的細胞株及肝組織切片法來篩選新的抗病毒的藥物。本研究證實了原本用於治療利什曼病（leishmaniasis）的一種藥物，sodium stibogluconate，可有效的抑制HCV的複製。此外我們又將Sip-L及CD81 cDNA基因轉染至老鼠的肝癌細胞Hepa1-6中，並證實此改造過的老鼠肝癌細胞可被C型肝炎病毒感染。

關鍵字

C型肝炎，細胞株

並列摘要

Hepatitis C Virus (HCV) is a member of the family Flaviviridae. It is the major causative agent of parenterally transmitted non-A non-B hepatitis. HCV infection may lead to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Previously, we have identified a hepatic factor capable of supporting HCV replication in an otherwise nonpermissive cell line, 293 EBNA cells. This factor exhibits homology to a group of protein derived from various evolutionarily distant species, including Oryza sativa submergence-induced protein 2A, temporarily named“submergence induced protein-like factor ”(Sip-L). We have utilized 293EBNA-Sip-L system and a newly developed human liver slice method to test for anti-viral activities of several candidate agents. Sodium stibogluconate, previously used to treat leshimaniasis, was found to be capable of suppressing HCV replication. Subsequently, we have transfected Hepa1-6 cells (mouse hepatoma cells) with CD81 and Sip-L cDNA genes. The transfected cells became permissive for HCV infection and replication.

並列關鍵字

Cell line ； HCV

參考文獻

Alter, M. J., Holland, P. V., Mprrpw, A. G., Purcell, R. H., Feinstone, S. M., and Moritsugu, Y. (1975). Clinical and serological analysis of transfusion-transmitted hepatitis. Lancet. 2, 838-841

Agnello, V., Abel, G., Elfahal, M., Knight, G. B. and Zhang, Q.-X. (1999). Hepatitis C virus and other Flaviviridae viruses entercells via low density lipoprotein receptor. Proc. Natl. Acad. Sci. USA 96, 12766-12771

Alter, M. J. (1997). Epidemiology of hepatitis C. Hepatology 26, 62S-65S

Bartenschlager, R., Lohmann, V. (2001). Novel cell culture systems for the hepatitis C Virus. Antiviral Research 52, 1-17

Bisceglie, A. M. D., McHutchison, J., and Rice, C. M. (2002). New Therapeutic Strategies for Hepatitis C. Hepatology 35, 224-231

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建立一個真實的C型肝炎病毒感染及複製系統

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