Project 2: Studies of biology of difficult-to-treat hepatitis C and development of novel strategies for its treatment
Project Leader: Prof. Jin ZHONG, Institut Pasteur of Shanghai, Chinese Academy of Sciences
Project No. 2008ZX10002-014
Hepatitis C virus (HCV) can cause acute and chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. China is one of high hepatitis C incidence areas, and has the biggest population of HCV infected patients in the world. Unfortunately, there is no vaccine to prevent HCV infection and no antiviral drug specifically against HCV at the present. PEG-interferon and ribavirin combination therapy, the only treatment against HCV now, is not satisfying for its efficacy, duration, cost and side-effects.
The overall objective of this grant is to uncover biological characteristics of difficult-to-treat hepatitis C, especially with Chinese isolates, and to explore the molecular mechanisms underlying viral pathogenesis and poor sustained virological response to the interferon therapy through studying virology, cell biology, immunology and clinical aspects of HCV infection, which would provide novel anti-viral drug targets and strategies for HCV treatment. For this aim, we will try to develop the molecular clones, cell culture models and small animal models for Chinese HCV isolates, and then establish advanced technical platforms for the antiviral drug and vaccine development with our own intellectual property. We hope that our research in this grant proposal will ultimately contribute to the prevention and treatment of hepatitis C in China.
Tongji Hospital of Huazhong University of Science and Technology
Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College
The No. Eighty-one Hospital, Chinese Liberation Army
1. Zhong B., Zhang L., Lei Z., Li Y., Mao A.P., Yang Y., Wang Y.Y., Zhang X.L., Shu H.B.* (2009). RNF5 negatively regulates virus-induced IRF3 activation via ubiquitination and degradation of MITA. Immunity 30:397-407.
2. Li Y., Li C., Xue P., Zhong B., Mao A.P., Ran Y., Chen H., Wang Y.Y., Yang F., Shu H.B.* (2009). ISG56 is a negative feedback regulator of virus-triggered signaling and cellular antiviral response. Proc. Natl. Acad. Sci. USA. 106:7945-7950.
3. Leiyun Weng, Jiamu Du, Jingling Zhou, Jianping Ding, Takaji Wakita, Michinori Kohara, Tetsuya Toyoda*. (2009). Modification of hepatitis C virus 1b RNA polymerase to make high-active JFH1 type polymerase by mutation of thumb domain. Arch. Virol. 154:765-773.
4. Tao, W., Xu, C., Ding, Q., Li, R., Xiang, Y., Chung, J., and Zhong, J. * (2009) A Single Point Mutation in E2 Enhances Hepatitis C Virus Infectivity and Alters Lipoprotein Association of Viral Particles. Virology, 395, 67–76.
5. Song X, Guo Y, Duo S, Che J, Wu C, Ochiya T, Ding M, Deng H. * (2009) A mouse model of inducible liver injury caused by tet-on regulated urokinase for studies of hepatocyte transplantation. Am J Pathol. 175(5):1975-83.
6. Song Zhihua, Cai Jun, Liu Yanxia, Zhao Dongxin, Yong Jun, Duo Shuguang, Song Xijun, Guo Yushan, Zhao Yang, Qin Han, Yin Xiaolei, Wu Chen, Che Jie, Ding Mingxiao, Deng Hongkui*. (2009) Efficient Generation of Hepatocyte-Like Cells from Human Induced Pluripotent Stem Cells. Cell Res. 19(11):1233-42.
7. Zhao D, Chen S, Cai J, Guo Y, Song Z, Che J, Liu C, Wu C, Ding M and Deng H*. (2009) Derivation and characterization of hepatic progenitor cells from human embryonic stem cells. PLoS One. 4(7):e6468.