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National Science and Technology Key Projects on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment”

Project 1: The Establishment of Detection Platform for Viral Infection and Immune Response in the Respiratory System and the Central Nerve System

Project leader: Ke Lan*
*Institut Pasteur of Shanghai,Chinese Academy of Sciences

Project profile:
Project number: 2009ZX10004-105
Validity: 2009/01---2010/12

Infectious diseases have been a growing severe menace to the public health and national security. In the recent thirty years, more than forty new pathogens have been identified and most of them are viruses. To date, infectious diseases have been the disease with the highest incidence in the world and they were the second cause to more than 50 million deaths globally each year. They damaged human's health, largely hampered and even destroyed developments of economy and society. In case of epidemic, fast and precise identification of pathogen is crucial to the control of disease. 

Development of platform for pathogen identification based on high-throughput technology will facilitate the prevention and control of disease. To develop such platform, different technologies on virology, genomics, bioinformatics, immunology and other domains should be integrated. The aim of the project is to associate experts from different fields and set up a platform to detect the viruses causing infections in respiratory tract and central nerve system. The project will later provide the base for the following expansion of the platform.

Cooperate Partners
Shanghai Municipal Center for Disease Control and Prevention
Beijing Ditan Hospital
Second Military Medical University
Zhejiang University
The Academy of Military Medical Science
Shanghai Center for Bioinformation Technology
Chinese National Human Genome Center at Shanghai

Published Articles
1. Xiuying Liu, Tianyi Wang, Takaji Wakita and Wei Yang.Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology,In Press, Corrected Proof, Available online 14 December 2009.
2. Ting Huang, Wei Wang, Mael Bessaud, Peijun Ren, Jun Sheng, Huajie Yan, Jing Zhang, XinLin, Yongjin Wang, Francis Delpeyroux, Vincent Deubel. Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection. PLoS ONE. July 2009, Volume 4, Issue 7.
3. Cheguo Tsai, Catherine Caillet, Hongxing Hu, Fan Zhou, Heng Ding, Guoliang Zhang, Boping Zhou, Shixia Wang, Shan Lu, Philippe Buchy, Vincent Deubel, Frederick R. Vogel, Paul Zhou. Measurement of neutralizing antibody responses against H5N1 clades in immunized mice and ferrets using pseudotypes expressing influenza hemagglutinin and neuraminidase.Vaccine 27 (2009) 6777–6790.
4.  Xinhui Lou, Yi Xiao, Yi Wang, Hongju Mao, and Jianlong Zhao. Label-Free Colorimetric Screening of Nuclease Activity and Substrates by Using Unmodified Gold Nanoparticles. ChemBioChem 2009, 10, 1973 – 1977.


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 profile:
Project No. 2008ZX10002-014
Validity: 2008/10---2010/12

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.

Cooperate Partners:
Beijing University
Wuhan University
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

Published Articles
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.

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