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Journal of Zhejiang University SCIENCE B 2005 Vol.6 No.4 P.295-300

http://doi.org/10.1631/jzus.2005.B0295


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


Author(s):  YAN Xue-bing, CHEN Zhi, LUO Dong-hui, XU Xiao-yan, WU Wei, ZHOU Lin-fu

Affiliation(s):  Institute of Infectious Diseases, First Affiliated Hospital, Key Laboratory of Health Ministry, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   yxb007@hotmail.com, chenzhi@zju.edu.cn

Key Words:  Hepatitis C virus, Core protein, Apoptosis, Necrosis


YAN Xue-bing, CHEN Zhi, LUO Dong-hui, XU Xiao-yan, WU Wei, ZHOU Lin-fu. Proapoptotic and pronecrosis effect of different truncated hepatitis C virus core proteins[J]. Journal of Zhejiang University Science B, 2005, 6(4): 295-300.

@article{title="Proapoptotic and pronecrosis effect of different truncated hepatitis C virus core proteins",
author="YAN Xue-bing, CHEN Zhi, LUO Dong-hui, XU Xiao-yan, WU Wei, ZHOU Lin-fu",
journal="Journal of Zhejiang University Science B",
volume="6",
number="4",
pages="295-300",
year="2005",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.2005.B0295"
}

%0 Journal Article
%T Proapoptotic and pronecrosis effect of different truncated hepatitis C virus core proteins
%A YAN Xue-bing
%A CHEN Zhi
%A LUO Dong-hui
%A XU Xiao-yan
%A WU Wei
%A ZHOU Lin-fu
%J Journal of Zhejiang University SCIENCE B
%V 6
%N 4
%P 295-300
%@ 1673-1581
%D 2005
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2005.B0295

TY - JOUR
T1 - Proapoptotic and pronecrosis effect of different truncated hepatitis C virus core proteins
A1 - YAN Xue-bing
A1 - CHEN Zhi
A1 - LUO Dong-hui
A1 - XU Xiao-yan
A1 - WU Wei
A1 - ZHOU Lin-fu
J0 - Journal of Zhejiang University Science B
VL - 6
IS - 4
SP - 295
EP - 300
%@ 1673-1581
Y1 - 2005
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2005.B0295


Abstract: 
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 C191 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.

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Reference

[1] Delhem, N., Sabile, A., Gajardo, R., Podevin, P., Abadie, A., Balton, M.A., Kremsdorf, D., Bretta, L., Brechot, C., 2000. Activation of the interferon-inducible protein kinase PKR by hepatocelluar carcinoma derived-hepatitis C virus CORE protein. Oncogene, 20:5836-5845.

[2] Francois, C., Duverlie, G., Rebouillat, D., Khorsi, H., Castelain, S., Blum, H.E., Gatignol, A., Wychowski, C., Moradpour, D., Meurs, E.F., 2000. Expression of hepatitis C virus proteins interferes with the antiviral action of interferon independently of PKR-mediated control of protein synthesis. J Virol., 74:5587-5596.

[3] Hope, R.G., McLauchlan, J., 2000. Sequence motifs required for lipid droplet association and protein stability are unique to the hepatitis C virus CORE protein. J Gen Virol., 81:1913-1925.

[4] Jin, D.Y., Wang, H.L., Zhou, Y., Chun, A.C., Kibler, K.V., Hou, Y.D., Kung, H., Jeang, K.T., 2000. Hepatitis C virus CORE protein-induced loss of LZIP function correlates with cellular transformation. EMBO J., 19(4):729-740.

[5] Kountouras, J., Zavos, C., Chatzopoulos, D., 2003. Apoptosis in hepatitis C. J Viral Hepat., 10(5):335-342.

[6] Naganuma, A., Nozaki, A., Tanaka, T., Sugiyama, K., Takagi, H., Mori, M., Shimotohno, K., Kato, N., 2000. Activation of the interferon-inducible 2-5-oligoadenylate synethase gene by hepatitis C virus CORE protein. J Virol., 74:8744-8750.

[7] Otsuka, M., Kato, N., Taniguchi, H., Yoshida, H., Goto, T., Shiratori, Y., Omata, M., 2002. Hepatitis C virus CORE protein inhibits apoptosis via enhanced Bcl-xL expression. Virology, 296:84-93.

[8] Ray, R.B., Ray, R., 2001. Hepatitis C virus CORE protein: intriguing properties and functional relevance. FEMS Microbiol Lett., 202:149-156.

[9] Realdon, S., Gerotto, M., Dal Pero, F., Marin, O., Granato, A., Basso, G., Muraca, M., Alberti, A., 2004. Proapoptotic effect of hepatitis C virus CORE protein in transiently transfected cells is enhanced by nuclear localization and is dependent on PKR activation. J Hepatol., 40:77-85.

[10] Sabile, A., Perlemuter, G., Bono, F., Kohara, K., Demaugre, F., Kohara, M., Matsuura, Y., Miyamura, T., Brechot, C., Barba, G., 1999. Hepatitis C virus CORE protein binds to apolipoprotein AII and its secretion is modulated by fibrates. Hepatology, 30:1064-1076.

[11] Schwer, B., Ren, S., Pietschmann, T., Kartenbeck, J., Kaehlcke, K., Bartenschlager, R., Yen, T.S., Ott, M., 2004. Targeting of hepatitis C virus core protein to mitochondria through a novel C-terminal localization motif. J Virol., 78(15):7958-7968.

[12] Suzuki, R., Suzuki, T., Ishii, K., Matsuura, Y., Miyamura, T., 1999. Processing and functions of hepatitis C virus proteins (review). Intervirology, 42:145-152.

[13] Taylor, D.R., Shi, S.T., Romano, P.R., Barber, G.N., Lai, M.M., 1999. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science, 285(5424):107-110.

[14] Xu, Z., Choi, J., Lu, W., Ou, J.H., 2003. Hepatitis C virus f protein is a short-lived protein associated with the endoplasmic reticulum. J Virol., 77(2):1578-1583.

[15] Yamanaka, T., Kodama, T., Doi, T., 2002. Subcellular localization of HCV CORE protein regulates its ability for p53 activation and p21 suppression. Biochem Biophys Res Commun, 294:528-534.

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