Rational design of a CD4 mimic that inhibits HIV-1 entry and exposes cryptic neutralization epitopes

Nature Biotechnology

Volumn 21, Issue 1, 2003, Pages 71-76

  Martin, Loïc ^a   Stricher, François ^a   Missé, Dorothée ^b   Sironi, Francesca ^c   Pugnière, Martine ^d   Barthe, Philippe ^d   Prado Gotor, Rafael ^d   Freulon, Isabelle ^a   Magne, Xavier ^b   Roumestand, Christian ^d   Ménez, André ^a   Lusso, Paolo ^c   Veas, Francisco ^b   Vita, Claudio ^a  

^a CEA SACLAY   (France)

^b INSTITUT DE RECHERCHE POUR LE DÉVELOPPEMENT   (France)

^c SAN RAFFAELE HOSPITAL   (Italy)

^d UNIV MONTPELLIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; ANTIBODIES; CELLS;

HUMAN IMMUNODEFICIENCY VIRUSES;

BIOTECHNOLOGY;

ANTIBODY; ANTIVIRUS AGENT; CD4 ANTIGEN; ENVELOPE PROTEIN; EPITOPE; GLYCOPROTEIN GP 120; VACCINE;

AMINO ACID SEQUENCE; ANTIVIRAL ACTIVITY; ARTICLE; BACTERIOPHAGE; BINDING AFFINITY; CELL IMMORTALIZATION; CELL ISOLATION; CONTROLLED STUDY; DRUG FORMULATION; HELA CELL; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING; RECEPTOR BINDING; SOLUBILITY; VIRUS ENVELOPE; VIRUS INHIBITION; VIRUS PARTICLE;

ANTIGENS, CD4; EPITOPES; HELA CELLS; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP120; HIV-1; HUMANS; MOLECULAR MIMICRY; PROTEIN CONFORMATION; PROTEOMICS; QUALITY CONTROL; SURFACE PLASMON RESONANCE; VIRION;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; RNA VIRUSES;

EID: 12244281787     PISSN: 10870156     EISSN: None     Source Type: Journal    
DOI: 10.1038/nbt768     Document Type: Article

References (45)

1. Kwong, P.D. et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing antibody. Nature 393, 648-659 (1998).
2. Kwong, P.D. et al. Structures of HIV-1 gp120 Envelope glycoproteins from laboratory adapted and primary isolates. Structure Fold. Des, 8, 1329-1339 (2000).
3. Wyatt, R. of et al. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393, 705-711 (1998).
4. Berger, E.A., Murphy, P.M. & Farber, J.M. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17, 657-700 (1999).
5. Wu, L. et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature 14, 179-183 (1996).
6. Trkola, A. et al. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 384, 184-187 (1996).
7. Rizzuto, C.D. et al. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280, 1949-1953 (1998).
8. Thali, M, et al. Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. J. Virol. 67, 3978-3988 (1993).
9. Sullivan, N. et al. CD4-Induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: Consequences for virus entry and neutralization. J. Virol. 72, 4694-4703 (1998).
10. Moulard, M. et al. Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120-CD4-CCR5 complexes. Proc. Natl. Acad. Sci. USA 99, 6913-6918 (2002).
11. Wyatt, R. & Sodroski, J. The HIV-1 envelope glycoproteins: Fusogens, antigens, and immunogens. Science 280, 1884-1888 (1998).
12. Kang, C.Y, Hariharan, K., Nara, P.L., Sodroski, J. & Moore, J. P. Immunization with a soluble CD4-gp120 complex preferentially induces neutralizing anti-human immunodeficiency virus type 1 antibodies directed to conformation-dependent epitopes of gp120. J. Virol. 68, 5854-5862 (1994).
13. DeVico, A., Silver, A., Thronton, A.M., Sarngadharan, M.G. & Pal, R. Covalently crosslinked complexes of human immunodeficiency virus type 1 (HIV-1) gp120 and CD4 receptor elicit a neutralizing immune response that includes antibodies selective for primary virus isolates. Virology 218, 258-263 (1996).
14. Fouts, T. et al. Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques. Proc. Natl. Acad. Sci. USA 99, 11842-11847 (2002).
15. Chan, D.C. & Kim, P.S. HIV entry and its inhibition. Cell 193, 681-684 (1998).
16. Eckert, D.M. & Kim, P.S. Mechanisms of viral membrane fusion and its inhibition. Annu. Rev. Biochem, 70, 777-810 (2001).
17. Gauduin, M.C. et al. Effective ex vivo neutralization of human Immunodeficiency virus type 1 in plasma by recombinant immunoglobulin molecules. J. Virol. 70, 2586-2592 (1996).
18. Allaway, G.P. et al. Expression and characterization of CD4-IgG2, a novel heterotetramer that neutralizes primary HIV type 1 isolates. AIDS Res. Hum. Retroviruses 11, 533-539 (1995).
19. Arthos, J. et al. Biochemical and biological characterization of a dodecameric CD4-Ig fusion protein. J. Biol. Chem. 277, 11456-11464 (2002).
20. Trkola, A. et al. Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG. J. Virol. 69, 6609-6617 (1995).
21. Drakopoulou, E., Vizzavona, J. & Vita, C. Engineering a CD4 mimetic inhibiting the binding of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120 to human lymphocyte CD4 by the transfer of a CD4 functional site to a small natural scaffold. Lett. Pep. Sci. 5, 241-245 (1998).
22. Zhang, W. et al. Conformational changes of gp120 in epitopes near the CCR5 binding site are induced by CD4 and a CD4 miniprotein mimetic. Biochemistry 38, 9405-9416 (1999).
23. Vita, C. et al. Rational engineering of a miniprotein that reproduces the core of the CD4 site interacting with HIV-1 envelope glycoprotein. Proc. Natl. Acad. Sci. USA 96, 13091-13096 (1999).
24. Vita, C., Roumestand, C., Toma, F. & Ménez, A. Scorpion toxins as natural scaffolds for protein engineering. Proc. Natl. Acad. Sci. USA 92, 6404-6408 (1995).
25. Martin, L., Barthe, P., Combes, O., Roumestand, C. & Vita, C. Engineering novel bioactive mini-proteins on natural scaffolds. Tetrahedron 56, 9451-9460 (2000).
26. Myszka, D.G. et al. Energetics of the HIV gp120-CD4 binding reaction. Proc. Natl. Acad. Sci. USA 97, 9026-9031 (2000).
27. Wu, H. et al. Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding. Proc. Natl. Acad. Sci. USA 93, 15030-15035 (1996).
28. Scarlatti, G. et al. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nat. Med. 11, 1259-1265 (1997).
29. Salzwedel, K., Smith, E.D., Dey, B, & Berger, E.A. Sequential CD4-corecepter interactions in human immunodeficiency virus type 1 Env function: Soluble CD4 activates Env for coreceptor-dependent fusion and reveals blocking activities of antibodies against cryptic conserved epitopes on gp120. J. Virol. 74, 326-333 (2000).
30. Rossio, J.L. et al. Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J. Virol. 72, 7992-8001 (1998).
31. Kwong, P.D., Wyatt, R., Sattentau, Q.J., Sodroski, J. & Hendrickson, W.A. Oligomeric modeling and electrostatic analysis of the gp120 envelope glycoprotein of human immunodeficiency virus. J. Virol. 74, 1961-1972 (2000).
32. Daar, E.S., Li, X.L., Moudgil, T. & Ho, D.D. High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates. Proc Natl Acad Sci USA 87, 6574-6578 (1990).
33. Shearer, W.T. et al. Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: Phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team. J. Infect. Dis. 182, 1774-1779 (2000).
34. Kilby, J.M. et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat. Med. 4, 1302-1307 (1998).
35. Little, S.J. et al. Reduced antiretroviral drug susceptibility among patients with primary HIV infection. JAMA 282, 1142-1149 (1999).
36. Solomon, H. et al. Prevalence of HIV-1 resistant to antiretroviral drugs in 81 individuals newly infected by sexual contact or injecting drug use. Investigators of the Quebec Primary Infection Study. AIDS 14, F17-23 (2000).
37. Wüthrich, K. NMR of Proteins and Nucleic Acids (Wiley, New York, 1986).
38. Guntert, P., Mumenthaler, C. & Wüthrich, K. Torsion angle dynamics for NMR structure calculation with the new program DYANA. J. Mol. Biol. 273, 283-298 (1997).
39. Koradi, R., Billeter, M. & Wüthrich, K. MOLMOL: a program for display and analysis of macromolecular structures. J. Mol. Graphics 14, 51-55 (1996).
40. Moore, J.P. Simple methods for monitoring HIV-1 and HIV-2 gp120 binding to sCD4 by ELISA: HIV-2 has a 25-fold lower affinity than HIV-1 for sCD4. AIDS 4, 297-303 (1990).
41. Martin, L. et al. Structural and functional analysis of the RANTES-glycosaminoglycans interactions. Biochemistry 40, 6303-6318 (2001).
42. Samson, M., Labbe, O., Mollereau, C., Vassart, G. & Parmentier, M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 35, 3362-3367 (1996).
43. Charneau, P. et al. HIV-1 reverse transcription. A termination step at the center of the genome. J. Mol. Biol. 241, 651-662 (1994).
44. Misse, D. et al. Dissociation of the CD4 and CXCR4 binding properties of human immunodeficiency virus type 1 gp120 by deletion of the first putative α-helical conserved structure. J. Virol. 72, 7280-7288 (1998).
45. +, T-cell clone (PM1): Failure to downregulate CD4 and to interfere with cell-line-tropic HIV-1. J. Virol. 69, 3712-3720 (1995).