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. 1992 Sep;66(9):5610–5614. doi: 10.1128/jvi.66.9.5610-5614.1992

Multimeric CD4 binding exhibited by human and simian immunodeficiency virus envelope protein dimers.

P L Earl 1, R W Doms 1, B Moss 1
PMCID: PMC289124  PMID: 1501294

Abstract

The envelope (Env) glycoproteins of human and simian immunodeficiency viruses (HIV and SIV) form noncovalently associated oligomers which mediate virus binding to the cell surface and fusion between the viral envelope and plasma membrane. A high-affinity interaction with CD4 is a critical step in this process. In this report, we show that Env protein dimers, but not monomers, can bind two CD4 molecules simultaneously. Multimeric CD4 binding may have important implications for Env protein-CD4 avidity, CD4-induced release of gp120, and subunit-subunit cooperativity during virus membrane fusion as well as for therapeutic strategies.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ada G. L. Vaccination and the immune response. Curr Biol. 1991 Aug;1(4):221–223. doi: 10.1016/0960-9822(91)90062-2. [DOI] [PubMed] [Google Scholar]
  2. Allan J. S., Strauss J., Buck D. W. Enhancement of SIV infection with soluble receptor molecules. Science. 1990 Mar 2;247(4946):1084–1088. doi: 10.1126/science.2309120. [DOI] [PubMed] [Google Scholar]
  3. Berger E. A., Fuerst T. R., Moss B. A soluble recombinant polypeptide comprising the amino-terminal half of the extracellular region of the CD4 molecule contains an active binding site for human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2357–2361. doi: 10.1073/pnas.85.7.2357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berger E. A., Lifson J. D., Eiden L. E. Stimulation of glycoprotein gp120 dissociation from the envelope glycoprotein complex of human immunodeficiency virus type 1 by soluble CD4 and CD4 peptide derivatives: implications for the role of the complementarity-determining region 3-like region in membrane fusion. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8082–8086. doi: 10.1073/pnas.88.18.8082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bosch M. L., Earl P. L., Fargnoli K., Picciafuoco S., Giombini F., Wong-Staal F., Franchini G. Identification of the fusion peptide of primate immunodeficiency viruses. Science. 1989 May 12;244(4905):694–697. doi: 10.1126/science.2541505. [DOI] [PubMed] [Google Scholar]
  6. Boulay F., Doms R. W., Webster R. G., Helenius A. Posttranslational oligomerization and cooperative acid activation of mixed influenza hemagglutinin trimers. J Cell Biol. 1988 Mar;106(3):629–639. doi: 10.1083/jcb.106.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chakrabarti S., Mizukami T., Franchini G., Moss B. Synthesis, oligomerization, and biological activity of the human immunodeficiency virus type 2 envelope glycoprotein expressed by a recombinant vaccinia virus. Virology. 1990 Sep;178(1):134–142. doi: 10.1016/0042-6822(90)90386-6. [DOI] [PubMed] [Google Scholar]
  8. Doms R. W., Earl P. L., Chakrabarti S., Moss B. Human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus env proteins possess a functionally conserved assembly domain. J Virol. 1990 Jul;64(7):3537–3540. doi: 10.1128/jvi.64.7.3537-3540.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Earl P. L., Doms R. W., Moss B. Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1990 Jan;87(2):648–652. doi: 10.1073/pnas.87.2.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Earl P. L., Koenig S., Moss B. Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses. J Virol. 1991 Jan;65(1):31–41. doi: 10.1128/jvi.65.1.31-41.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Earl P. L., Moss B., Doms R. W. Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. J Virol. 1991 Apr;65(4):2047–2055. doi: 10.1128/jvi.65.4.2047-2055.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Freed E. O., Myers D. J., Risser R. Characterization of the fusion domain of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4650–4654. doi: 10.1073/pnas.87.12.4650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hart T. K., Kirsh R., Ellens H., Sweet R. W., Lambert D. M., Petteway S. R., Jr, Leary J., Bugelski P. J. Binding of soluble CD4 proteins to human immunodeficiency virus type 1 and infected cells induces release of envelope glycoprotein gp120. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2189–2193. doi: 10.1073/pnas.88.6.2189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hurtley S. M., Helenius A. Protein oligomerization in the endoplasmic reticulum. Annu Rev Cell Biol. 1989;5:277–307. doi: 10.1146/annurev.cb.05.110189.001425. [DOI] [PubMed] [Google Scholar]
  15. Kirsh R., Hart T. K., Ellens H., Miller J., Petteway S. A., Jr, Lambert D. M., Leary J., Bugelski P. J. Morphometric analysis of recombinant soluble CD4-mediated release of the envelope glycoprotein gp120 from HIV-1. AIDS Res Hum Retroviruses. 1990 Oct;6(10):1209–1212. doi: 10.1089/aid.1990.6.1209. [DOI] [PubMed] [Google Scholar]
  16. Koenig S., Hirsch V. M., Olmsted R. A., Powell D., Maury W., Rabson A., Fauci A. S., Purcell R. H., Johnson P. R. Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2443–2447. doi: 10.1073/pnas.86.7.2443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
  18. Layne S. P., Merges M. J., Dembo M., Spouge J. L., Nara P. L. HIV requires multiple gp120 molecules for CD4-mediated infection. Nature. 1990 Jul 19;346(6281):277–279. doi: 10.1038/346277a0. [DOI] [PubMed] [Google Scholar]
  19. McCune J. M., Rabin L. B., Feinberg M. B., Lieberman M., Kosek J. C., Reyes G. R., Weissman I. L. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell. 1988 Apr 8;53(1):55–67. doi: 10.1016/0092-8674(88)90487-4. [DOI] [PubMed] [Google Scholar]
  20. McKeating J. A., Willey R. L. Structure and function of the HIV envelope. AIDS. 1989;3 (Suppl 1):S35–S41. doi: 10.1097/00002030-198901001-00005. [DOI] [PubMed] [Google Scholar]
  21. Mizukami T., Fuerst T. R., Berger E. A., Moss B. Binding region for human immunodeficiency virus (HIV) and epitopes for HIV-blocking monoclonal antibodies of the CD4 molecule defined by site-directed mutagenesis. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9273–9277. doi: 10.1073/pnas.85.23.9273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moore J. P., McKeating J. A., Huang Y. X., Ashkenazi A., Ho D. D. Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J Virol. 1992 Jan;66(1):235–243. doi: 10.1128/jvi.66.1.235-243.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moore J. P., McKeating J. A., Norton W. A., Sattentau Q. J. Direct measurement of soluble CD4 binding to human immunodeficiency virus type 1 virions: gp120 dissociation and its implications for virus-cell binding and fusion reactions and their neutralization by soluble CD4. J Virol. 1991 Mar;65(3):1133–1140. doi: 10.1128/jvi.65.3.1133-1140.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Moore J. P., McKeating J. A., Weiss R. A., Sattentau Q. J. Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science. 1990 Nov 23;250(4984):1139–1142. doi: 10.1126/science.2251501. [DOI] [PubMed] [Google Scholar]
  25. Pinter A., Honnen W. J., Tilley S. A., Bona C., Zaghouani H., Gorny M. K., Zolla-Pazner S. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J Virol. 1989 Jun;63(6):2674–2679. doi: 10.1128/jvi.63.6.2674-2679.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  27. Rey M. A., Krust B., Laurent A. G., Montagnier L., Hovanessian A. G. Characterization of human immunodeficiency virus type 2 envelope glycoproteins: dimerization of the glycoprotein precursor during processing. J Virol. 1989 Feb;63(2):647–658. doi: 10.1128/jvi.63.2.647-658.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rey M. A., Laurent A. G., McClure J., Krust B., Montagnier L., Hovanessian A. G. Transmembrane envelope glycoproteins of human immunodeficiency virus type 2 and simian immunodeficiency virus SIV-mac exist as homodimers. J Virol. 1990 Feb;64(2):922–926. doi: 10.1128/jvi.64.2.922-926.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rose J. K., Doms R. W. Regulation of protein export from the endoplasmic reticulum. Annu Rev Cell Biol. 1988;4:257–288. doi: 10.1146/annurev.cb.04.110188.001353. [DOI] [PubMed] [Google Scholar]
  30. Ryu S. E., Kwong P. D., Truneh A., Porter T. G., Arthos J., Rosenberg M., Dai X. P., Xuong N. H., Axel R., Sweet R. W. Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature. 1990 Nov 29;348(6300):419–426. doi: 10.1038/348419a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sanjuan A., Quesneau Y., Delagneau J. F., Brun-Vezinet F. Value of HIV transmembrane glycoprotein oligomers as target antigens in early detection of anti-env antibodies. AIDS Res Hum Retroviruses. 1991 Oct;7(10):789–790. doi: 10.1089/aid.1991.7.789. [DOI] [PubMed] [Google Scholar]
  32. Sattentau Q. J., Moore J. P. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. J Exp Med. 1991 Aug 1;174(2):407–415. doi: 10.1084/jem.174.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schawaller M., Smith G. E., Skehel J. J., Wiley D. C. Studies with crosslinking reagents on the oligomeric structure of the env glycoprotein of HIV. Virology. 1989 Sep;172(1):367–369. doi: 10.1016/0042-6822(89)90142-6. [DOI] [PubMed] [Google Scholar]
  34. Thomas D. J., Wall J. S., Hainfeld J. F., Kaczorek M., Booy F. P., Trus B. L., Eiserling F. A., Steven A. C. gp160, the envelope glycoprotein of human immunodeficiency virus type 1, is a dimer of 125-kilodalton subunits stabilized through interactions between their gp41 domains. J Virol. 1991 Jul;65(7):3797–3803. doi: 10.1128/jvi.65.7.3797-3803.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wang J. H., Yan Y. W., Garrett T. P., Liu J. H., Rodgers D. W., Garlick R. L., Tarr G. E., Husain Y., Reinherz E. L., Harrison S. C. Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature. 1990 Nov 29;348(6300):411–418. doi: 10.1038/348411a0. [DOI] [PubMed] [Google Scholar]
  36. Weiss C. D., Levy J. A., White J. M. Oligomeric organization of gp120 on infectious human immunodeficiency virus type 1 particles. J Virol. 1990 Nov;64(11):5674–5677. doi: 10.1128/jvi.64.11.5674-5677.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Willey R. L., Klimkait T., Frucht D. M., Bonifacino J. S., Martin M. A. Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing. Virology. 1991 Sep;184(1):319–329. doi: 10.1016/0042-6822(91)90848-6. [DOI] [PubMed] [Google Scholar]

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