教育经历
工作经历
研究概述
发表文章
李文辉 博士
北京生命科学研究所资深研究员
Wenhui Li, Ph.D. Investigator, NIBS, Beijing, China
Phone：-8580
Fax：
E-mail：liwenhui@nibs.ac.cn
教育经历
Education
1994
兰州大学医学院 医学学士学位
Bachelor Degree of Medicine
1997
兰州生物制品研究所 免疫学硕士学位
Lanzhou Institute of Biological Products
M.S. in Immunology
2001
中国协和医科大学中国医学科学院 病原生物学博士学位
Ph.D. in Pathogens Biology
工作经历
Professional Experience
2015.3-
北京生命科学研究所资深研究员
Investigator, National Institute of Biological Sciences,
Beijing
2007.10-2015.2
北京生命科学研究所研究员
Assistant Investigator, National Institute of Biological Sciences,
Beijing
2004.6-2007.9
哈佛大学医学院 Instructor
Harvard MedicalSchool,Boston
2001.9-2004.5
哈佛大学医学院 博士后
Postdoctoral Fellow,HarvardMedicalSchool,Boston
研究概述
Research Description
本实验室的研究兴趣集中于重要病毒感染的分子机制及其防治。近年来，我们主要致力于乙肝病毒（HBV）研究。乙型肝炎是危害人类健康的严重传染病。全球估计有HBV感染者2.4亿人，其中我国约有9300****。慢性HBV感染是导致肝硬化、肝癌的重要病因。丁型肝炎病毒（HDV）是HBV的卫星病毒,在所有HBV感染者中，约有1500****同时感染HDV。我们发现HBV及HDV感染肝细胞的关键受体是钠离子-牛磺胆酸共转运蛋白（NTCP）；稳定表达人NTCP的HepG2细胞系(HepG2-NTCP)已成为HBV相关基础病毒学研究和抗病毒药物研发的重要平台。目前，对乙肝感染的科学研究及药物开发已进入一个充满生机的新时代。本实验室综合运用病毒学，生物化学，免疫学，化学生物学等多学科方法深入剖析HBV及HDV感染过程的分子基础，以帮助理解其病理机制。我们也希望研发新的抗病毒药物，为最终有效解除患者的病痛而努力。此外，我们也与相关实验室合作研究NTCP/胆酸等分子在感染及机体代谢过程中的相关作用。
Our laboratory is interested in studying molecular mechanisms of viral infection and developing antiviral interventions. We’ve been focused on hepatitis B virus (HBV) in recent years. HBV infection remains a public health problem. About 240 million people are infected by HBV worldwide and among them 93 million are in China. Chronic HBV infection is a major cause of cirrhosis and hepatocellular carcinoma. Hepatitis D virus (HDV), a satellite of HBV, infects 15 million people among those infected by HBV. We identified sodium taurocholatecotransporting polypeptide (NTCP), a liver bile acid transporter, as a crucial receptor for viral infection of HBV and HDV; Human hepatoma HepG2 cell complemented with human NTCP (HepG2-NTCP) has become an important platform for studying HBV basic virology and developing antivirals. The field is entering into a new era of vibrant research of the virus and towards developing a cure for the infection. Our laboratory combines virology, biochemistry, immunology, and chemical biology to investigate molecular mechanisms of HBV/HDV infection. Our research will help to elucidate the pathogenesis of the viruses and to develop new drugs for the treatment of the infection and associated diseases. We also collaborate with other colleagues to study NTCP/bile acids for their roles in the infection and related metabolic process.
发表文章
Publications：
1.
He, W.,B.Ren, F.Mao,Z.Jing,Y.Li,Y.Liu,B.Peng, H. Yan,Y.Qi,Y.Sun, J-T.Guo,J.Sui,F.Wang, andW.Li*. Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide.PLOS Pathog, 10.1371/journal.ppat.**, 2015.
2.
Yan, H., B. Peng, Y. Liu, G. Xu, W. He, B. Ren, Z. Jing, J. Sui, and W. Li*. Viral entry of hepatitis B and d viruses and bile salts transportation share common molecular determinants on sodium taurocholatecotransporting polypeptide. Journal of virology, 88(6): p. 3273-84, 2014.
3.
Sun, Y*., Y. Qi, C. Liu, W. Gao, P. Chen, L. Fu, B. Peng, H. Wang, Z. Jing, G. Zhong, and W. Li*. Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus. Journal of virology, 88(1):237-48, 2014.
4.
Xu, G., Z. Gao, W. He, Y. Ma, X. Feng, T. Cai, F. Lu, L. Liu, and W. Li*. microRNA expression in hepatitis B virus infected primary treeshrew hepatocytes and the independence of intracellular miR-122 level for de novo HBV infection in culture. Virology, 448: 247-54, 2014.
5.
Zhong, G., H. Yan, H. Wang, W. He, Z. Jing, Y. Qi, L. Fu, Z. Gao, Y. Huang, G. Xu, X. Feng, J. Sui, and W. Li*. Sodium taurocholatecotransporting polypeptide mediates woolly monkey hepatitis B virus infection of Tupaia hepatocytes. Journal of virology, 87(12): 7176-84, 2013.
6.
Yan, H., B. Peng, W. He, G. Zhong, Y. Qi, B. Ren, Z. Gao, Z. Jing, M. Song, G. Xu, J. Sui, and W. Li*. Molecular determinants of hepatitis B and D virus entry restriction in mouse sodium taurocholatecotransporting polypeptide. Journal of virology, 87(14): 7977-91, 2013.
7.
Liu, F., M. Campagna, Y. Qi, X. Zhao, F. Guo, C. Xu, S. Li, W. Li, T.M. Block, J. Chang, and J.T. Guo*. Alpha-interferon suppresses hepadnavirus transcription by altering epigenetic modification of cccDNAminichromosomes.PLoSPathog, 9(9): p. e**, 2013.
8.
Lin, S., H. Yan, L. Li, M. Yang, B. Peng, S. Chen, W. Li*, and P.R. Chen*. Site-Specific Engineering of Chemical Functionalities on the Surface of Live Hepatitis D Virus. AngewandteChemie International Edition, 52(52): 13970-13974, 2013.
9.
Jemielity, S., J.J. Wang, Y.K. Chan, A.A. Ahmed, W. Li, S. Monahan, X. Bu, M. Farzan, G.J. Freeman, D.T. Umetsu, R.H. Dekruyff, and H. Choe*. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoSPathog, 9(3): e**, 2013.
10.
Yan, H., G. Zhong, G. Xu, W. He, Z. Jing, Z. Gao, Y. Huang, Y. Qi, B. Peng, H. Wang, L. Fu, M. Song, P. Chen, W. Gao, B. Ren, Y. Sun, T. Cai, X. Feng, J. Sui, and W. Li*. Sodium taurocholatecotransporting polypeptide is a functional receptor for human hepatitis B and D virus.eLife, 1: e00049, 2012.
11.
Chen, P., Z. Song, Y. Qi, X. Feng, N. Xu, Y. Sun, X. Wu, X. Yao, Q. Mao, X. Li, W. Dong, X. Wan, N. Huang, X. Shen, Z. Liang, and W. Li*. Molecular determinants of enterovirus 71 viral entry: cleft around GLN-172 on VP1 protein interacts with variable region on scavenge receptor B 2. J BiolChem, 287(9): 6406-20, 2012.
12.
Huang, Z., Y. Feng, D. Chen, X. Wu, S. Huang, X. Wang, X. Xiao, W. Li, N. Huang, L. Gu, G. Zhong, and J. Chai*. Structural basis for activation and inhibition of the secreted chlamydia protease CPAF. Cell Host Microbe, 4(6):529-42, 2008.
13.
Huang, I.-C., W. Li, J. Sui, W. Marasco, H. Choe, and M. Farzan*. Influenza A virus neuraminidase limits viral superinfection. Journal of virology, 82(10): 4834-4843, 2008.
14.
Radoshitzky, S.R., J. Abraham, C.F. Spiropoulou, J.H. Kuhn, D. Nguyen, W. Li, J. Nagel, P.J. Schmidt, J.H. Nunberg, N.C. Andrews, M. Farzan, and H. Choe*. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature, 446(7131): p. 92-6, 2007.
15.
Li, W., J. Sui, I. Huang, J.H. Kuhn, S.R. Radoshitzky, W.A. Marasco, H. Choe, and M. Farzan*. The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology, 367(2): 367-374, 2007.
16.
Zhang, L., F. Zhang, W. Yu, T. He, J. Yu, C.E. Yi, L. Ba, W. Li, M. Farzan, Z. Chen, K.Y. Yuen, and D. Ho*. Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals. J Med Virol, 78(1): 1-8, 2006.
17.
Li, F., M. Berardi, W. Li, M. Farzan, P.R. Dormitzer, and S.C. Harrison*. Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain. Journal of virology, 80(14): 6794-6800, 2006.
18.
Kuhn, J.H., S.R. Radoshitzky, A.C. Guth, K.L. Warfield, W. Li, M.J. Vincent, J.S. Towner, S.T. Nichol, S. Bavari, H. Choe, M.J. Aman, and M. Farzan*. Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor. J BiolChem, 2006. 281(23): 15951-8.
19.
Huang, I.-C., B.J. Bosch, F. Li, W. Li, K.H. Lee, S. Ghiran, N. Vasilieva, T.S. Dermody, S.C. Harrison, and P.R. Dormitzer*. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J BiolChem, 281(6): 3198-3203, 2006.
20.
He, Y., J. Li, W. Li, S. Lustigman, M. Farzan, and S. Jiang*. Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. Journal of Immunology, 176(10): 6085-6092, 2006.
21.
Sui, J., W. Li, A. Roberts, L.J. Matthews, A. Murakami, L. Vogel, S.K. Wong, K. Subbarao, M. Farzan, and W.A. Marasco*. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. Journal of virology, 79(10): 5900-5906, 2005.
22.
Li, W., C. Zhang, J. Sui, J.H. Kuhn, M.J. Moore, S. Luo, S.K. Wong, I.C. Huang, K. Xu, N. Vasilieva, A. Murakami, Y. He, W.A. Marasco, Y. Guan, H*. Choe*, and M. Farzan*. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J, 24(8): 1634-43, 2005.
23.
Li, F., W. Li, M. Farzan, and S.C. Harrison*. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 309(5742): 1864-1868, 2005.
24.
Choe, H., M.J. Moore, C.M. Owens, P.L. Wright, N. Vasilieva, W. Li, A.P. Singh, R. Shakri, C.E. Chitnis, and M. Farzan*. Sulphatedtyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC). Molecular microbiology, 55(5): 1413-1422, 2005.
25.
Wong, S.K., W. Li, M.J. Moore, H. Choe, and M. Farzan*. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem,279(5): 3197-3201, 2004.
26.
Sui, J., W. Li, A. Murakami, A. Tamin, L.J. Matthews, S.K. Wong, M.J. Moore, A.S. Tallarico, M. Olurinde, H. Choe, L.J. Anderson, W.J. Bellini, M. Farzan, and W.A. Marasco*. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl AcadSci U S A, 101(8): 2536-41, 2004.
27.
Moore, M.J., T. Dorfman, W. Li, S.K. Wong, Y. Li, J.H. Kuhn, J. Coderre, N. Vasilieva, Z. Han, T.C. Greenough, M. Farzan, and H. Choe*. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. Journal of virology, 78(19):10628-35, 2004.
28.
Li, W., T.C. Greenough, M.J. Moore, N. Vasilieva, M. Somasundaran, J.L. Sullivan, M. Farzan*, and H. Choe*. Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2. Journal of virology, 78(20):11429-11433, 2004.
29.
He, Y., Y. Zhou, S. Liu, Z. Kou, W. Li, M. Farzan, and S. Jiang*. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine. Biochemical and biophysical research communications, 324(2): 773-781, 2004.
30.
Li, W., M.J. Moore, N. Vasilieva, J. Sui, S.K. Wong, M.A. Berne, M. Somasundaran, J.L. Sullivan, K. Luzuriaga, T.C. Greenough, H. Choe*, and M. Farzan*. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 426(6965): 450-454, 2003.
31.
Choe, H., W. Li, P.L. Wright, N. Vasilieva, M. Venturi, C.C. Huang, C. Grundner, T. Dorfman, M.B. Zwick, L. Wang, E.S. Rosenberg, P.D. Kwong, D.R. Burton, J.E. Robinson, J.G. Sodroski, and M. Farzan*. Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120. Cell, 114(2): 161-170, 2003.
32.
Farzan, M., S. Chung, W. Li, N. Vasilieva, P.L. Wright, C.E. Schnitzler, R.J. Marchione, C. Gerard, N.P. Gerard, and J. Sodroski*. Tyrosine-sulfated peptides functionally reconstitute a CCR5 variant lacking a critical amino-terminal region. J BiolChem, 277(43):40397-40402, 2002.
33.
Li, W.,Y. Zhang,J.Sui, S. Wang *. Combined immunization of DNA vaccine and replication-defective recombinant adenovirus bearing rabies glycoprotein gene induces immune response against rabies virus. Chin J Micro and Immuno, 22(4): 403-406,2002 (in Chinese)
34.
Sui, J.,W.Li, X.Jiang, Y. He,Z. Song*. Highly Efficient Expression and Functional Studies of An Anti-KG1a Cell scFv 5C1 derived from Phage Display Antibody Library. Chin J Micro and Immuno, 21(4) : 437~441,2001 (in Chinese)
35.
Li, W., Y. Zhang, S. Wang*, L. Liu. Immune response of mice against replication-defective recombinant adenovirus containing glycoprotein gene of rabies 3aG strain. Chin J Exp and Clin Viro,15(1):35-39,2001 (in Chinese)
36.
Li, W., S. Wang*, Y. Zhang, L.Liu. Construction of cloned recombinant adenovirus genome by homologous recombination in Escherichia coli. Chin JBiochem and Mole Bio, 16(3):346-35,2000 (in Chinese)
37.
Zhang, X., Y. Zhang, W. Li, S. Wang*.Expression of glycoprotein gene of the rabies virus 3aG strain by E-3 deleted adenovirus recombinant. Chin J of Exp and ClinViro, 14 (3).281-284, 2000 (in Chinese)
受邀综述
Invited Review Articles:
1.
Li, W. Hepatitis B virus receptor, Annual Review of Cell and Developmental Biology,doi/abs/10.1146, 2015.
2.
Yan, H and W.Li*. NTCP acts as a receptor for hepatitis B and D virus,Digestive DiseasesClinical Reviews,doi:10.1159/,2015.
3.
Watashi*, K., S. Urban, W. Li, and T. Wakita. NTCP and Beyond: Opening the Door to Unveil Hepatitis B Virus Entry. Int J MolSci, 15(2): p.2892-905, 2014.
4.
Li, W*, S.-K. Wong, F. Li, J.H. Kuhn, I.-C. Huang, H. Choe, and M. Farzan*. Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions. Journal of virology, 80(9): 4211-4219, 2006.
5.
Kuhn, J., W. Li, H. Choe, and M. Farzan*. Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus. Cellular and molecular life sciences: 61(21): 2738-2743, 2004.
