CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5 (original) (raw)

Nature volume 384, pages 179–183 (1996)Cite this article

Abstract

FOR efficient entry into target cells, primary macrophage-tropic and laboratory-adapted human immunodeficiency viruses type 1 (HIV-1) require particular chemokine receptors, CCR-5 and CXCR-4, respectively, as well as the primary receptor CD4 (refs 1–6). Here we show that a complex of gp120, the exterior envelope glycoprotein, of macrophage-tropic primary HIV-1 and soluble CD4 interacts specifically with CCR-5 and inhibits the binding of the natural CCR-5 ligands, macrophage inflammatory protein (MIP)-1α and MIP-1β (refs 7, 8). The apparent affinity of the interaction between gp120 and CCR-5 was dramatically lower in the absence of soluble CD4. Additionally, in the absence of gp120, an interaction between a two-domain CD4 fragment and CCR-5 was observed. A gp120 fragment retaining the CD4-binding site and overlapping epitopes was able to interact with CCR-5 only if the V3 loop, which can specify HIV-1 tropism and chemokine receptor choice2,9–11, was also present on the molecule. Neutralizing antibodies directed against either CD4-induced or V3 epitopes on gp120 blocked the interaction of gp120-CD4 complexes with CCR-5. These results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Feng, Y., Broder, C. C., Kennedy, P. E. & Berger, E. A. Science 272, 872–877 (1996).
    Article ADS CAS PubMed Google Scholar
  2. Choe, H. et al. Cell 85, 1135–1148 (1996).
    Article CAS PubMed Google Scholar
  3. Doranz, B. J. et al. Cell 85, 1149–1158 (1996).
    Article CAS PubMed Google Scholar
  4. Dragic, T. et al. Nature 381, 667–673 (1996).
    Article ADS CAS PubMed Google Scholar
  5. Deng, H. et al. Nature 381, 661–666 (1996).
    Article ADS CAS PubMed Google Scholar
  6. Akhatib, G. et al. Science 272, 1955–1958 (1996).
    Article ADS Google Scholar
  7. Samson, M. et al. Biochemistry 35, 3362–3367 (1996).
    Article CAS PubMed Google Scholar
  8. Raport, C. et al. J. Biol. Chem. 271, 17161–17166 (1996).
    Article CAS PubMed Google Scholar
  9. Cheng-Mayer, C. et al. J. Virol. 64, 4390–4398 (1990).
    CAS PubMed PubMed Central Google Scholar
  10. Chesebro, B. et al. J. Virol. 65, 5782–5789 (1991).
    CAS PubMed PubMed Central Google Scholar
  11. Hwang, S. et al. Science 253, 71–74 (1991).
    Article ADS CAS PubMed Google Scholar
  12. Arthos, J. et al. Cell 57, 469–481 (1989).
    Article CAS PubMed Google Scholar
  13. Helseth, E., Olshevsky, U., Furman, C. & Sodroski, J. J. Virol. 65, 2119–2123 (1991).
    CAS PubMed PubMed Central Google Scholar
  14. Wyatt, R. et al. J. Virol. 67, 4557–4565 (1993).
    CAS PubMed PubMed Central Google Scholar
  15. Wyatt, R. et al. J. Virol. 69, 5723–5733 (1995).
    CAS PubMed PubMed Central Google Scholar
  16. Ivey-Hoyie, M. et al. Proc. Natl Acad. Sci. USA 88, 512–516 (1991).
    Article ADS Google Scholar
  17. Posner, M. et al. J. Immunol. 146, 4325–4332 (1991).
    CAS PubMed Google Scholar
  18. Thali, M. et al. J. Virol. 67, 3978–3988 (1993).
    CAS PubMed PubMed Central Google Scholar
  19. Moore, J. & Sodroski, J. J. Virol. 70, 1863–1872 (1996).
    CAS PubMed PubMed Central Google Scholar
  20. Gershoni, J. et al. FASEB J. 7, 1185–1187 (1993).
    Article CAS PubMed Google Scholar
  21. Moore, J. et al. J. Virol. 69, 122–130 (1995).
    CAS PubMed PubMed Central Google Scholar
  22. Burkly, L. et al. J. Immunol. 149, 1779–1787 (1992).
    CAS PubMed Google Scholar
  23. Healey, D. et al. J. Exp. Med. 172, 1233–1242 (1990).
    Article CAS PubMed Google Scholar
  24. Truneh, A. et al. J. Biol. Chem. 266, 5942–5948 (1991).
    CAS PubMed Google Scholar
  25. Bachelder, R., Bilancieri, J., Lin, W. & Letvin, N. J. Virol. 69, 5734–5742 (1995).
    CAS PubMed PubMed Central Google Scholar
  26. Sullivan, N., Sun, Y., Li, J., Hoffman, W. & Sodroski, J. J. Virol. 69, 4413–4422 (1995).
    CAS PubMed PubMed Central Google Scholar
  27. Ponath, P., Qin, S., Post, T. et al. J. Exp. Med. 183, 2437–2448 (1996).
    Article CAS PubMed Google Scholar
  28. Culp, J. S., Johansen, H., Hellmig, B. et al. Biotechnology 9, 173–177 (1991).
    CAS PubMed Google Scholar
  29. Gerard, N. P., Hodges, M. K., Drazen, J. M., Weller, P. F. & Gerard, C. J. Biol. Chem. 264, 1760–1766 (1989).
    CAS PubMed Google Scholar

Download references

Author information

Authors and Affiliations

  1. LeukoSite, Inc., 215 First Street, Cambridge, Massachusetts, 02142, USA
    Lijun Wu, Nancy Ruffing & Walter Newman
  2. Perlmutter Laboratory, Children's Hospital, and Departments of Medicine and Pediatrics, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA
    Norma P. Gerard & Craig Gerard
  3. Division of Human Retroviorology, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Richard Wyatt, Hyeryun Choe, Alessândra Borsetti, Elizabeth Desjardin & Joseph Sodroski
  4. Institute of Microbiology, University of Padua, Padua, 35121, Italy
    Cristina Parolin
  5. Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts, 02115, USA
    Angelo A. Cardoso
  6. Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts, 02115, USA
    Joseph Sodroski

Authors

  1. Lijun Wu
    You can also search for this author inPubMed Google Scholar
  2. Norma P. Gerard
    You can also search for this author inPubMed Google Scholar
  3. Richard Wyatt
    You can also search for this author inPubMed Google Scholar
  4. Hyeryun Choe
    You can also search for this author inPubMed Google Scholar
  5. Cristina Parolin
    You can also search for this author inPubMed Google Scholar
  6. Nancy Ruffing
    You can also search for this author inPubMed Google Scholar
  7. Alessândra Borsetti
    You can also search for this author inPubMed Google Scholar
  8. Angelo A. Cardoso
    You can also search for this author inPubMed Google Scholar
  9. Elizabeth Desjardin
    You can also search for this author inPubMed Google Scholar
  10. Walter Newman
    You can also search for this author inPubMed Google Scholar
  11. Craig Gerard
    You can also search for this author inPubMed Google Scholar
  12. Joseph Sodroski
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Wu, L., Gerard, N., Wyatt, R. et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5.Nature 384, 179–183 (1996). https://doi.org/10.1038/384179a0

Download citation