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. 1992 Sep;66(9):5516–5524. doi: 10.1128/jvi.66.9.5516-5524.1992

Lack of correlation between soluble CD4-induced shedding of the human immunodeficiency virus type 1 exterior envelope glycoprotein and subsequent membrane fusion events.

M Thali 1, C Furman 1, E Helseth 1, H Repke 1, J Sodroski 1
PMCID: PMC289110  PMID: 1501286

Abstract

The noncovalent association of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) is disrupted by soluble CD4 binding, resulting in shedding of the gp120 exterior envelope glycoprotein. This observation has led to the speculation that interaction of gp120 with the CD4 receptor triggers shedding of the exterior envelope glycoprotein, allowing exposure of gp41 domains necessary for membrane fusion steps involved in virus entry or syncytium formation. To test this hypothesis, a set of HIV-1 envelope glycoprotein mutants were used to examine the relationship of soluble CD4-induced shedding of the gp120 glycoprotein to envelope glycoprotein function in syncytium formation and virus entry. All mutants with a threefold or greater reduction in CD4-binding ability exhibited marked decreases in gp120 shedding in response to soluble CD4, even though several of these mutants exhibited significant levels of envelope glycoprotein function. Conversely, most fusion-defective mutants with wild-type gp120-CD4 binding affinity, including those with changes in the V3 loop, efficiently shed gp120 following soluble CD4 binding. Thus, soluble CD4-induced shedding of gp120 is not a generally useful marker for conformational changes in the HIV-1 envelope glycoproteins necessary for the virus entry or syncytium formation processes. Some gp120 mutants, despite being expressed on the cell surface and capable of efficiently binding soluble CD4, exhibited decreased gp120 shedding. These mutants were still sensitive to neutralization by soluble CD4, indicating that, for envelope glycoproteins exhibiting high affinity for soluble CD4, competitive inhibition may be more important than gp120 shedding for the antiviral effect.

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Selected References

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  1. Allan J. S., Coligan J. E., Barin F., McLane M. F., Sodroski J. G., Rosen C. A., Haseltine W. A., Lee T. H., Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985 May 31;228(4703):1091–1094. doi: 10.1126/science.2986290. [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. Arthos J., Deen K. C., Chaikin M. A., Fornwald J. A., Sathe G., Sattentau Q. J., Clapham P. R., Weiss R. A., McDougal J. S., Pietropaolo C. Identification of the residues in human CD4 critical for the binding of HIV. Cell. 1989 May 5;57(3):469–481. doi: 10.1016/0092-8674(89)90922-7. [DOI] [PubMed] [Google Scholar]
  4. Ashkenazi A., Presta L. G., Marsters S. A., Camerato T. R., Rosenthal K. A., Fendly B. M., Capon D. J. Mapping the CD4 binding site for human immunodeficiency virus by alanine-scanning mutagenesis. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7150–7154. doi: 10.1073/pnas.87.18.7150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Autiero M., Abrescia P., Dettin M., Di Bello C., Guardiola J. Binding to CD4 of synthetic peptides patterned on the principal neutralizing domain of the HIV-1 envelope protein. Virology. 1991 Dec;185(2):820–828. doi: 10.1016/0042-6822(91)90553-n. [DOI] [PubMed] [Google Scholar]
  6. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Bergeron L., Sullivan N., Sodroski J. Target cell-specific determinants of membrane fusion within the human immunodeficiency virus type 1 gp120 third variable region and gp41 amino terminus. J Virol. 1992 Apr;66(4):2389–2397. doi: 10.1128/jvi.66.4.2389-2397.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bowman M. R., MacFerrin K. D., Schreiber S. L., Burakoff S. J. Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1990 Nov;87(22):9052–9056. doi: 10.1073/pnas.87.22.9052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brighty D. W., Rosenberg M., Chen I. S., Ivey-Hoyle M. Envelope proteins from clinical isolates of human immunodeficiency virus type 1 that are refractory to neutralization by soluble CD4 possess high affinity for the CD4 receptor. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7802–7805. doi: 10.1073/pnas.88.17.7802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Brodsky M. H., Warton M., Myers R. M., Littman D. R. Analysis of the site in CD4 that binds to the HIV envelope glycoprotein. J Immunol. 1990 Apr 15;144(8):3078–3086. [PubMed] [Google Scholar]
  13. Bugelski P. J., Ellens H., Hart T. K., Kirsh R. L. Soluble CD4 and dextran sulfate mediate release of gp120 from HIV-1: implications for clinical trials. J Acquir Immune Defic Syndr. 1991;4(9):923–924. [PubMed] [Google Scholar]
  14. Callahan L. N., Phelan M., Mallinson M., Norcross M. A. Dextran sulfate blocks antibody binding to the principal neutralizing domain of human immunodeficiency virus type 1 without interfering with gp120-CD4 interactions. J Virol. 1991 Mar;65(3):1543–1550. doi: 10.1128/jvi.65.3.1543-1550.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Choe H. R., Sodroski J. Contribution of charged amino acids in the CDR2 region of CD4 to HIV-1 gp120 binding. J Acquir Immune Defic Syndr. 1992;5(2):204–210. [PubMed] [Google Scholar]
  16. Clayton L. K., Hussey R. E., Steinbrich R., Ramachandran H., Husain Y., Reinherz E. L. Substitution of murine for human CD4 residues identifies amino acids critical for HIV-gp120 binding. Nature. 1988 Sep 22;335(6188):363–366. doi: 10.1038/335363a0. [DOI] [PubMed] [Google Scholar]
  17. Cordonnier A., Montagnier L., Emerman M. Single amino-acid changes in HIV envelope affect viral tropism and receptor binding. Nature. 1989 Aug 17;340(6234):571–574. doi: 10.1038/340571a0. [DOI] [PubMed] [Google Scholar]
  18. Cordonnier A., Rivière Y., Montagnier L., Emerman M. Effects of mutations in hyperconserved regions of the extracellular glycoprotein of human immunodeficiency virus type 1 on receptor binding. J Virol. 1989 Oct;63(10):4464–4468. doi: 10.1128/jvi.63.10.4464-4468.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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 U S A. 1990 Sep;87(17):6574–6578. doi: 10.1073/pnas.87.17.6574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  21. Deen K. C., McDougal J. S., Inacker R., Folena-Wasserman G., Arthos J., Rosenberg J., Maddon P. J., Axel R., Sweet R. W. A soluble form of CD4 (T4) protein inhibits AIDS virus infection. Nature. 1988 Jan 7;331(6151):82–84. doi: 10.1038/331082a0. [DOI] [PubMed] [Google Scholar]
  22. Fauci A. S., Macher A. M., Longo D. L., Lane H. C., Rook A. H., Masur H., Gelmann E. P. NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med. 1984 Jan;100(1):92–106. doi: 10.7326/0003-4819-100-1-92. [DOI] [PubMed] [Google Scholar]
  23. Fisher R. A., Bertonis J. M., Meier W., Johnson V. A., Costopoulos D. S., Liu T., Tizard R., Walker B. D., Hirsch M. S., Schooley R. T. HIV infection is blocked in vitro by recombinant soluble CD4. Nature. 1988 Jan 7;331(6151):76–78. doi: 10.1038/331076a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Freed E. O., Myers D. J., Risser R. Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain. J Virol. 1991 Jan;65(1):190–194. doi: 10.1128/jvi.65.1.190-194.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  27. Grimaila R. J., Fuller B. A., Rennert P. D., Nelson M. B., Hammarskjöld M. L., Potts B., Murray M., Putney S. D., Gray G. Mutations in the principal neutralization determinant of human immunodeficiency virus type 1 affect syncytium formation, virus infectivity, growth kinetics, and neutralization. J Virol. 1992 Apr;66(4):1875–1883. doi: 10.1128/jvi.66.4.1875-1883.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Helseth E., Kowalski M., Gabuzda D., Olshevsky U., Haseltine W., Sodroski J. Rapid complementation assays measuring replicative potential of human immunodeficiency virus type 1 envelope glycoprotein mutants. J Virol. 1990 May;64(5):2416–2420. doi: 10.1128/jvi.64.5.2416-2420.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Helseth E., Olshevsky U., Furman C., Sodroski J. Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein. J Virol. 1991 Apr;65(4):2119–2123. doi: 10.1128/jvi.65.4.2119-2123.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Helseth E., Olshevsky U., Gabuzda D., Ardman B., Haseltine W., Sodroski J. Changes in the transmembrane region of the human immunodeficiency virus type 1 gp41 envelope glycoprotein affect membrane fusion. J Virol. 1990 Dec;64(12):6314–6318. doi: 10.1128/jvi.64.12.6314-6318.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Hussey R. E., Richardson N. E., Kowalski M., Brown N. R., Chang H. C., Siliciano R. F., Dorfman T., Walker B., Sodroski J., Reinherz E. L. A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. Nature. 1988 Jan 7;331(6151):78–81. doi: 10.1038/331078a0. [DOI] [PubMed] [Google Scholar]
  33. Ivanoff L. A., Looney D. J., McDanal C., Morris J. F., Wong-Staal F., Langlois A. J., Petteway S. R., Jr, Matthews T. J. Alteration of HIV-1 infectivity and neutralization by a single amino acid replacement in the V3 loop domain. AIDS Res Hum Retroviruses. 1991 Jul;7(7):595–603. doi: 10.1089/aid.1991.7.595. [DOI] [PubMed] [Google Scholar]
  34. Ivey-Hoyle M., Culp J. S., Chaikin M. A., Hellmig B. D., Matthews T. J., Sweet R. W., Rosenberg M. Envelope glycoproteins from biologically diverse isolates of immunodeficiency viruses have widely different affinities for CD4. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):512–516. doi: 10.1073/pnas.88.2.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jameson B. A., Rao P. E., Kong L. I., Hahn B. H., Shaw G. M., Hood L. E., Kent S. B. Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein. Science. 1988 Jun 3;240(4857):1335–1339. doi: 10.1126/science.2453925. [DOI] [PubMed] [Google Scholar]
  36. Javaherian K., Langlois A. J., McDanal C., Ross K. L., Eckler L. I., Jellis C. L., Profy A. T., Rusche J. R., Bolognesi D. P., Putney S. D. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768–6772. doi: 10.1073/pnas.86.17.6768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  38. Kowalski M., Bergeron L., Dorfman T., Haseltine W., Sodroski J. Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein. J Virol. 1991 Jan;65(1):281–291. doi: 10.1128/jvi.65.1.281-291.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Landau N. R., Warton M., Littman D. R. The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4. Nature. 1988 Jul 14;334(6178):159–162. doi: 10.1038/334159a0. [DOI] [PubMed] [Google Scholar]
  41. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  42. Leonard C. K., Spellman M. W., Riddle L., Harris R. J., Thomas J. N., Gregory T. J. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990 Jun 25;265(18):10373–10382. [PubMed] [Google Scholar]
  43. Lifson J. D., Feinberg M. B., Reyes G. R., Rabin L., Banapour B., Chakrabarti S., Moss B., Wong-Staal F., Steimer K. S., Engleman E. G. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature. 1986 Oct 23;323(6090):725–728. doi: 10.1038/323725a0. [DOI] [PubMed] [Google Scholar]
  44. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  45. Matsushita S., Robert-Guroff M., Rusche J., Koito A., Hattori T., Hoshino H., Javaherian K., Takatsuki K., Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. doi: 10.1128/jvi.62.6.2107-2114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  47. McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
  48. McKeating J., Balfe P., Clapham P., Weiss R. A. Recombinant CD4-selected human immunodeficiency virus type 1 variants with reduced gp120 affinity for CD4 and increased cell fusion capacity. J Virol. 1991 Sep;65(9):4777–4785. doi: 10.1128/jvi.65.9.4777-4785.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. 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]
  51. 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]
  52. 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]
  53. Mulligan M. J., Ritter G. D., Jr, Chaikin M. A., Yamshchikov G. V., Kumar P., Hahn B. H., Sweet R. W., Compans R. W. Human immunodeficiency virus type 2 envelope glycoprotein: differential CD4 interactions of soluble gp120 versus the assembled envelope complex. Virology. 1992 Mar;187(1):233–241. doi: 10.1016/0042-6822(92)90311-c. [DOI] [PubMed] [Google Scholar]
  54. Olshevsky U., Helseth E., Furman C., Li J., Haseltine W., Sodroski J. Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. J Virol. 1990 Dec;64(12):5701–5707. doi: 10.1128/jvi.64.12.5701-5707.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Page K. A., Stearns S. M., Littman D. R. Analysis of mutations in the V3 domain of gp160 that affect fusion and infectivity. J Virol. 1992 Jan;66(1):524–533. doi: 10.1128/jvi.66.1.524-533.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Posner M. R., Hideshima T., Cannon T., Mukherjee M., Mayer K. H., Byrn R. A. An IgG human monoclonal antibody that reacts with HIV-1/GP120, inhibits virus binding to cells, and neutralizes infection. J Immunol. 1991 Jun 15;146(12):4325–4332. [PubMed] [Google Scholar]
  57. Putney S. D., Matthews T. J., Robey W. G., Lynn D. L., Robert-Guroff M., Mueller W. T., Langlois A. J., Ghrayeb J., Petteway S. R., Jr, Weinhold K. J. HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope. Science. 1986 Dec 12;234(4782):1392–1395. doi: 10.1126/science.2431482. [DOI] [PubMed] [Google Scholar]
  58. Robey W. G., Safai B., Oroszlan S., Arthur L. O., Gonda M. A., Gallo R. C., Fischinger P. J. Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science. 1985 May 3;228(4699):593–595. doi: 10.1126/science.2984774. [DOI] [PubMed] [Google Scholar]
  59. Rusche J. R., Javaherian K., McDanal C., Petro J., Lynn D. L., Grimaila R., Langlois A., Gallo R. C., Arthur L. O., Fischinger P. J. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A. 1988 May;85(9):3198–3202. doi: 10.1073/pnas.85.9.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. 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]
  61. 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]
  62. Skinner M. A., Langlois A. J., McDanal C. B., McDougal J. S., Bolognesi D. P., Matthews T. J. Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J Virol. 1988 Nov;62(11):4195–4200. doi: 10.1128/jvi.62.11.4195-4200.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Smith D. H., Byrn R. A., Marsters S. A., Gregory T., Groopman J. E., Capon D. J. Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen. Science. 1987 Dec 18;238(4834):1704–1707. doi: 10.1126/science.3500514. [DOI] [PubMed] [Google Scholar]
  64. Sodroski J., Goh W. C., Rosen C., Dayton A., Terwilliger E., Haseltine W. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986 May 22;321(6068):412–417. doi: 10.1038/321412a0. [DOI] [PubMed] [Google Scholar]
  65. Stegmann T., Doms R. W., Helenius A. Protein-mediated membrane fusion. Annu Rev Biophys Biophys Chem. 1989;18:187–211. doi: 10.1146/annurev.bb.18.060189.001155. [DOI] [PubMed] [Google Scholar]
  66. Stein B. S., Gowda S. D., Lifson J. D., Penhallow R. C., Bensch K. G., Engleman E. G. pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. Cell. 1987 Jun 5;49(5):659–668. doi: 10.1016/0092-8674(87)90542-3. [DOI] [PubMed] [Google Scholar]
  67. Thali M., Olshevsky U., Furman C., Gabuzda D., Li J., Sodroski J. Effects of changes in gp120-CD4 binding affinity on human immunodeficiency virus type 1 envelope glycoprotein function and soluble CD4 sensitivity. J Virol. 1991 Sep;65(9):5007–5012. doi: 10.1128/jvi.65.9.5007-5012.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Thali M., Olshevsky U., Furman C., Gabuzda D., Posner M., Sodroski J. Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody. J Virol. 1991 Nov;65(11):6188–6193. doi: 10.1128/jvi.65.11.6188-6193.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Traunecker A., Lüke W., Karjalainen K. Soluble CD4 molecules neutralize human immunodeficiency virus type 1. Nature. 1988 Jan 7;331(6151):84–86. doi: 10.1038/331084a0. [DOI] [PubMed] [Google Scholar]
  70. Travis B. M., Dykers T. I., Hewgill D., Ledbetter J., Tsu T. T., Hu S. L., Lewis J. B. Functional roles of the V3 hypervariable region of HIV-1 gp160 in the processing of gp160 and in the formation of syncytia in CD4+ cells. Virology. 1992 Jan;186(1):313–317. doi: 10.1016/0042-6822(92)90088-7. [DOI] [PubMed] [Google Scholar]
  71. 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]
  72. White J. M. Viral and cellular membrane fusion proteins. Annu Rev Physiol. 1990;52:675–697. doi: 10.1146/annurev.ph.52.030190.003331. [DOI] [PubMed] [Google Scholar]
  73. Wiley D. C., Skehel J. J. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem. 1987;56:365–394. doi: 10.1146/annurev.bi.56.070187.002053. [DOI] [PubMed] [Google Scholar]

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