Our lab tries to understand the entry mechanisms of enveloped viruses. Regardless of the type of enveloped virus, the initial step of viral entry always involves the interactions between the viral envelope protein(s) and viral receptor(s) on host cells. The questions that we are mostly interested in are: what is the specific cellular receptor for a virus? How does the receptor contribute to viral entry? How does the viral entry protein evade the host immune response? How can viral infection be inhibited by entry inhibitor or host immunity. We seek to identify the receptors and elucidate the entry processes of viral pathogens important to human health. Knowledge of viral entry mechanisms will deepen our understanding of basic biology of viruses and their host cells, and offer new opportunities to develop more efficient inhibitors against the infections and new generation of viral vaccines.
Hepatitis B virus (HBV) infection and its associated cirrhosis and hepatocellular carcinoma cause about one million deaths annually. The molecular mechanisms by which HBV and its satellite virus Hepatitis D virus (HDV) infect human liver have been elusive. By taking state-of-the-art affinity purification approach, we recently identified sodium taurocholate cotransporting polypeptide (NTCP), a liver bile acid transporter, as a specific receptor for HBV and HDV. NTCP binds to a critical receptor binding region of viral envelope L protein and contributes substantially to the efficiency of HBV and HDV infections. This finding advances our understanding of the HBV and HDV infection and may lead to new strategies for prevention and treatment of these viral infections and associated diseases.
发表文章
Publications
1.
Li W, Sui J, Huang IC, Kuhn JH, Radoshitzky SR, Marasco WA, Choe H, Farzan M.The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology. 2007; doi:10.1016/j.virol.2007.04.035
2.
Radoshitzky SR, Abraham J, Spiropoulou CF, Kuhn JH, Nguyen D, Li W, Nagel J, Schmidt PJ, Nunberg JH, Andrews NC, Farzan M, Choe H. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature. 2007;446(7131):92-6.
3.
Kuhn JH, Li W, Radoshitzky SR, Choe H, Farzan M. Severe acute respiratory syndrome coronavirus entry as a target of antiviral therapies. Antiviral Therapy. 2007, 12:639-650 review
4.
Li F, Berardi M, Li W, Farzan M, Dormitzer PR, Harrison SC. Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain. J Virol. 2006, 80(14): 6794-800.
5.
He Y, Li J, Li W, Lustigman S, Farzan M, Jiang S. Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. J Immunol. 2006,176(10):6085-92.
6.
Li W, Wong SK, Li F, Kuhn JH, Huang IC, Choe H, Farzan M. Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions. J Virol. 2006,80(9):4211-9 review
7.
Kuhn JH, Radoshitzky SR, Guth AC, Warfield KL, Li W, Vincent MJ, Towner JS, Nichol ST, Bavari S, Choe H, Aman MJ, Farzan M. Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor. J Biol Chem. 2006,281(23):15951-8.
8.
Huang IC, Bosch BJ, Li F, Li W, Lee KH, Ghiran S, Vasilieva N, Dermody TS, Harrison SC, Dormitzer PR, Farzan M, Rottier PJ, Choe H. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J Biol Chem. 2006,281(6):3198-203.
9.
Zhang L, Zhang F, Yu W, He T, Yu J, Yi CE, Ba L, Li W, Farzan M, Chen Z, Yuen KY, Ho D. Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals.J Med Virol. 2006,78(1):1-8.
10.
Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science. 2005,309(5742):1864-8. Comments in science. 2005, 16; 309 (5742) :1822-3.
11.
Sui J, Li W, Roberts A, Matthews LJ, Murakami A, Vogel L, Wong SK, Subbarao K, Farzan M, Marasco WA. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants.J Virol. 2005,79(10):5900-6.
12.
Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, Wong SK, Huang IC, Xu K, Vasilieva N, Murakami A, He Y, Marasco WA, Guan Y, Choe H, Farzan M. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 2005,24(8):1634-43.
13.
Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK, Moore MJ, Tallarico AS, Olurinde M, Choe H, Anderson LJ, Bellini WJ, Farzan M, Marasco WA. 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. 2004 ,101(8):2536-41.
14.
Wong SK, Li W, Moore MJ, Choe H, Farzan M.A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem. 2004, 279(5):3197-201.
15.
Moore MJ, Dorfman T, Li W, Wong SK, Li Y, Kuhn JH, Coderre J, Vasilieva N, Han Z, Greenough TC, Farzan M, Choe H. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. J Virol. 2004;78(19):10628-35.
16.
Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003, 426 (6965) :450-4. Comment in Cell. 2003,115(6):652-3
17.
Choe H, Li W, Wright PL, Vasilieva N, Venturi M, Huang CC, Grundner C, Dorfman T, Zwick MB, Wang L, Rosenberg ES, Kwong PD,Burton DR, Robinson JE, Sodroski JG, Farzan M.Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120. Cell. 2003,114(2):161-70. Comment in Cell. 2003,114(2):147-8.
18.
Farzan M, Chung S, Li W, Vasilieva N, Wright PL, Schnitzler CE, Marchione RJ, Gerard C, Gerard NP, Sodroski J, Choe H. Tyrosine-sulfated peptides functionally reconstitute a CCR5 variant lacking a critical amino-terminal region. J Biol Chem. 2002, 277(43):40397-402.
19.
Li W, Zhang Y, Sui J, Wang S. Combined immunization of DNA vaccine and replication-defective recombinant adenovirus bearing rabies glycoprotein gene induces immune response against rabies virus. Chinese Journal of Microbiology and Immunology,2002, 22(4): 403-406
20.
Sui J,Li W, Jiang X, He Y, Song Z. Highly Efficient Expression and Functional Studies of An Anti-KG1a Cell scFv 5C1 derived from Phage Display Antibody Library. Chinese Journal of Microbiology and Immunology. 2001, 21(4) : 437~441
21.
Li W, Zhang Y, Wang S, Liu L. Immune response of mice against replication-defective recombinant adenovirus containing glycoprotein gene of rabies 3aG strain. Chinese Journal of Experimental and Clinical Virology, 2001, 15(1):35-39
22.
Li W, Wang S, Zhang Y, Liu L. Construction of cloned recombinant adenovirus genome by homologous recombination in Escherichia coli. Chinese Journal of Biochemistry and Molecular Biology, 2000, 16(3):346-351
23.
Shen X, Xie Y, Li W . Construction of recombinant HBV preS2 -S Pichia pastoris. Progress in Microbiology and Immunology, 1999,27(1):14-18