Wenhui Li, Ph.D.

Assistant Investigator, NIBS, Beijing, China

Phone：010-80726688-8580

Fax： 010-80726689

E-mail：liwenhui@nibs.ac.cn

Education

Professional Experience

Research Description

We combine virology, biochemistry, chemical biology, immunology, and animal models to investigate molecular mechanisms of infection of Hepatitis B virus (HBV). HBV infection remains a public health problem worldwide. About 240 million people are affected by HBV. 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 taurocholate cotransporting polypeptide (NTCP), a liver bile acid transporter, as a crucial receptor for viral infection of HBV and HDV. This finding has significantly advanced our understanding on the tissue tropism, species specificity and infection mechanisms of HBV and HDV. The finding also provides a candidate intervention target, and has helped establish new HBV/HDV infection platforms for studying HBV biology, as well as developing new treatments against related diseases. Our long-term goal is to elucidate the pathogenesis of the viruses and to develop new drugs for the treatment of the infection and associated diseases.

Research Articles

1. He, W.,Z.Cao, F.Mao,B.Ren,Y. Li, B.Peng, H. Yan, Y.Qi, Y.Sun, F.Wang, J.Sui*, W.Li*. Modification of Three Amino Acids in Sodium Taurocholate Cotransporting Polypeptide Renders Mice Susceptible to Infection with Hepatitis D Virus In Vivo. J Virol, 90(19):8866-74, 2016.

2. Qi, Y.,Z.Gao, G.Xu,B.Peng,C.Liu, H. Yan,Y. Qi,G.Sun,Y.Liu,D.Tang,Z.Song,W.He,Y.Sun, J-T.Guo, W.Li*. DNA polymerase κ is a key cellular factor for the formation of covalently closed circular DNA of hepatitis B virus. PLOS Pathog, 12(10):e1005893. doi: 10.1371 /journal.ppat.1005893,2016

3. 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, and W.Li*. Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide. PLOS Pathog, 11(4):e1004840. doi: 10.1371/journal.ppat.1004840,2015

4. 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 taurocholate cotransporting polypeptide. J Virol, 88(6): p. 3273-84, 2014.

5. 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. J Virol, 88(1):237-48, 2014.

6. 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.

7. 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 taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of Tupaia hepatocytes. J Virol, 87(12): 7176-84, 2013.

8. 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 taurocholate cotransporting polypeptide. J Virol, 87(14): 7977-91, 2013.

9. 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 cccDNA minichromosomes. PLoS Pathog, 9(9): p. e1003613, 2013.

10. 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. Angewandte Chemie International Edition, 52(52): 13970-13974, 2013.

11. 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. PLoS Pathog, 9(3): e1003232, 2013.

12. 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 taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife, 1: e00049, 2012.

13. 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 Biol Chem, 287(9): 6406-20, 2012.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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 Biol Chem, 2006. 281(23): 15951-8.

21. 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 Biol Chem, 281(6): 3198-3203, 2006.

22. 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. The Journal of Immunology, 176(10): 6085-6092, 2006.

23. 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.

24. 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.

25. 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.

26. 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*, Sulphated tyrosines 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.

27. 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.

28. 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 Acad Sci U S A, 101(8): 2536-41, 2004.

29. 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. J Virol, 78(19):10628-35, 2004.

30. 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. J virol, 78(20):11429-11433, 2004.

31. 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.

32. 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.

33. 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.

34. 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 Biol Chem, 277(43):40397-40402, 2002.

35. 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)

36. 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)

37. 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)

38. Li, W., S. Wang*, Y. Zhang, L.Liu, Construction of cloned recombinant adenovirus genome by homologous recombination in Escherichia coli. Chin J Biochem and Mole Bio, 16(3):346-35,2000 (in Chinese)

39. 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 Clin Viro, 14 (3).281-284, 2000 (in Chinese)

40. 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)

41. 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)

42. 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)

43. Li, W., S. Wang*, Y. Zhang, L.Liu, Construction of cloned recombinant adenovirus genome by homologous recombination in Escherichia coli. Chin J Biochem and Mole Bio, 16(3):346-35,2000 (in Chinese)

Invited Review Articles:

1. Li,W* and S.Urban*,  Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications. Journal of Hepatology,64(1 Suppl):S32-40, 2016

2. Li, W*. The hepatitis B virus receptor. Annu Rev Cell Dev Biol,31:125-47, 2015

3. Yan, H.,Y. Liu, J. Sui, W Li*, NTCP opens the door for hepatitis B virus infection, Antiviral research, 121:24-30,2015

4. Watashi*, K., S. Urban, W. Li, and T. Wakita, NTCP and Beyond: Opening the Door to Unveil Hepatitis B Virus Entry. Int J Mol Sci, 15(2): p.2892-905, 2014.

5. Xu,G.,W.He,Z.Jing,H.Yan,G.Zhong,and W.Li*, Identifying sodium taurocholate cotrans-porting polypeptide as a functional receptor of Hepatitis B and D virus. Chin J Micro and Immuno, 33(1):3-5, 2013 (in Chinese)

6. 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.