Archives of Virology

, Volume 159, Issue 3, pp 555–560 | Cite as

Structural requirements of glycosaminoglycans for their interaction with HIV-1 envelope glycoprotein gp120

  • Pedro M. Matos
  • David Andreu
  • Nuno C. Santos
  • Ricardo Gutiérrez-Gallego
Brief Report


Heparan sulfate proteoglycans are known to assist HIV-1 entry into host cells, mediated by the viral envelope glycoprotein gp120. We aimed to determine the general structural features of glycosaminoglycans that enable their binding to gp120, by surface plasmon resonance. Binding was found to be dependent on sequence type, size and sulfation patterns. HIV-1 gp120 prefers heparin and heparan sulfate (with at least 16 monomers in length) over chondroitin and dermatan. Sulfate groups were essential to promote this interaction. These results advance the understanding of the molecular-level requirements for virus attachment and cell entry.


HIV-1 gp120 Viral attachment Heparan sulfate proteoglycans Glycosaminoglycans Surface plasmon resonance 



This work was funded by Fundação para a Ciência e a Tecnologia–Ministério da Educação e Ciência (FCT-MEC, Portugal; projects PTDC/QUI-BIQ/104787/2008 and VIH/SAU/0047/2011, as well as P.M.M. PhD fellowship SFRH/BD/42205/2007) and the Spanish Ministry of Science and Innovation (project BIO2009-08983 to R.G.G.).


  1. 1.
    Klasse PJ (2012) The molecular basis of HIV entry. Cell Microbiol 14:1183–1192PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Melikyan GB (2011) Membrane fusion mediated by human immunodeficiency virus envelope glycoprotein. Curr Top Membr 68:81–106PubMedCrossRefGoogle Scholar
  3. 3.
    Ugolini S, Mondor I, Sattentau QJ (1999) HIV-1 attachment: another look. Trends Microbiol 7:144–149PubMedCrossRefGoogle Scholar
  4. 4.
    Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999) Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 68:729–777PubMedCrossRefGoogle Scholar
  5. 5.
    Esko JD, Kimata K, Lindahl U (2009) Proteoglycans and Sulfated Glycosaminoglycans. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME (eds) Essentials of Glycobiology. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  6. 6.
    Mbemba E, Czyrski JA, Gattegno L (1992) The interaction of a glycosaminoglycan, heparin, with HIV-1 major envelope glycoprotein. Biochim Biophys Acta 1180:123–129PubMedCrossRefGoogle Scholar
  7. 7.
    Roderiquez G, Oravecz T, Yanagishita M, Bou-Habib DC, Mostowski H, Norcross MA (1995) Mediation of human immunodeficiency virus type 1 binding by interaction of cell surface heparan sulfate proteoglycans with the V3 region of envelope gp120-gp41. J Virol 69:2233–2239PubMedCentralPubMedGoogle Scholar
  8. 8.
    Vives RR, Imberty A, Sattentau QJ, Lortat-Jacob H (2005) Heparan sulfate targets the HIV-1 envelope glycoprotein gp120 coreceptor binding site. J Biol Chem 280:21353–21357PubMedCrossRefGoogle Scholar
  9. 9.
    Crublet E, Andrieu JP, Vives RR, Lortat-Jacob H (2008) The HIV-1 envelope glycoprotein gp120 features four heparan sulfate binding domains, including the co-receptor binding site. J Biol Chem 283:15193–15200PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    de Parseval A, Bobardt MD, Chatterji A, Chatterji U, Elder JH, David G, Zolla-Pazner S, Farzan M, Lee TH, Gallay PA (2005) A highly conserved arginine in gp120 governs HIV-1 binding to both syndecans and CCR5 via sulfated motifs. J Biol Chem 280:39493–39504PubMedCrossRefGoogle Scholar
  11. 11.
    Mondor I, Ugolini S, Sattentau QJ (1998) Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4 independent and gp120 dependent and requires cell surface heparans. J Virol 72:3623–3634PubMedCentralPubMedGoogle Scholar
  12. 12.
    Zhang YJ, Hatziioannou T, Zang T, Braaten D, Luban J, Goff SP, Bieniasz PD (2002) Envelope-dependent, cyclophilin-independent effects of glycosaminoglycans on human immunodeficiency virus type 1 attachment and infection. J Virol 76:6332–6343PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Bobardt MD, Saphire AC, Hung HC, Yu X, Van der Schueren B, Zhang Z, David G, Gallay PA (2003) Syndecan captures, protects, and transmits HIV to T lymphocytes. Immunity 18:27–39PubMedCrossRefGoogle Scholar
  14. 14.
    Saphire AC, Bobardt MD, Zhang Z, David G, Gallay PA (2001) Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages. J Virol 75:9187–9200PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    de Witte L, Bobardt M, Chatterji U, Degeest G, David G, Geijtenbeek TB, Gallay P (2007) Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1. Proc Natl Acad Sci USA 104:19464–19469PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Gallay P (2004) Syndecans and HIV-1 pathogenesis. Microbes Infect 6:617–622PubMedCrossRefGoogle Scholar
  17. 17.
    Rider CC, Coombe DR, Harrop HA, Hounsell EF, Bauer C, Feeney J, Mulloy B, Mahmood N, Hay A, Parish CR (1994) Anti-HIV-1 activity of chemically modified heparins: correlation between binding to the V3 loop of gp120 and inhibition of cellular HIV-1 infection in vitro. Biochemistry 33:6974–6980PubMedCrossRefGoogle Scholar
  18. 18.
    Bishop JR, Schuksz M, Esko JD (2007) Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446:1030–1037PubMedCrossRefGoogle Scholar
  19. 19.
    Kato M, Wang H, Bernfield M, Gallagher JT, Turnbull JE (1994) Cell surface syndecan-1 on distinct cell types differs in fine structure and ligand binding of its heparan sulfate chains. J Biol Chem 269:18881–18890PubMedGoogle Scholar
  20. 20.
    Bobardt MD, Chatterji U, Schaffer L, de Witte L, Gallay PA (2010) Syndecan-Fc hybrid molecule as a potent in vitro microbicidal anti-HIV-1 agent. Antimicrob Agents Chemother 54:2753–2766PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Baleux F, Loureiro-Morais L, Hersant Y, Clayette P, Arenzana-Seisdedos F, Bonnaffe D, Lortat-Jacob H (2009) A synthetic CD4-heparan sulfate glycoconjugate inhibits CCR5 and CXCR4 HIV-1 attachment and entry. Nat Chem Biol 5:743–748PubMedCrossRefGoogle Scholar
  22. 22.
    Connell BJ, Baleux F, Coic YM, Clayette P, Bonnaffe D, Lortat-Jacob H (2012) A synthetic heparan sulfate-mimetic peptide conjugated to a mini CD4 displays very high anti- HIV-1 activity independently of coreceptor usage. Chem Biol 19:131–139PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Instituto de Medicina Molecular, Faculdade de MedicinaUniversidade de LisboaLisbonPortugal
  2. 2.Department of Experimental and Health SciencesPompeu Fabra UniversityBarcelonaSpain
  3. 3.Bio-analysis group, Neuroscience Research ProgramIMIM-Parc Salut MarBarcelonaSpain

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