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Volume 81, Issue 5

Properties of a neutralizing antibody that recognizes a conformational form of epitope ERDRD in the gp41 C-terminal tail of human immunodeficiency virus type 1 Free

Abstract

The possibility that epitopes from the C-terminal tail of the gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) are exposed the surface of the virion has long been contentious. Resolution of this has been hampered by the absence of any neutralizing monoclonal antibodies, but we have recently epitope-purified a neutralizing polyclonal IgG specific for one of the putative gp41 tail epitopes, ERDRD. This was obtained from mice immunized parenterally with a plant virus chimera expressing residues 731–752 from the gp41 tail. The ERDRD epitope is highly conformational and is conserved in 81% of B clade viruses. Here, it is shown that this polyclonal ERDRD-specific IgG is highly potent, with an affinity of 2·2×10 M, and a neutralization rate constant (− ) of 7·8×10 M s that exceeds that of nearly all other known HIV-1-neutralizing antibodies. ERDRD-specific IgG gave 50% neutralization at 0·1–0·2 μg/ml and 90% neutralization at approximately 3 μg/ml. It also neutralized virus that was already attached to target cells, and this and other data suggest that it neutralized by inhibiting a virion event that precedes the fusion–entry process. Consistent with this conclusion was the finding that neutralizing amounts of ERDRD-specific IgG did not inhibit the attachment of free virus to target cells. ERDRD-specific IgG was also cross-reactive and neutralized all but one of six B clade T cell line-adapted strains tested.

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2000-05-01
2024-04-19
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References

  1. Armstrong, S. J. & Dimmock, N. J. (1996). Varying temperature-dependence of post-attachment neutralization of human immunodeficiency virus type 1 by monoclonal antibodies to gp120: identification of a very early fusion-independent event as a neutralization target.Journal of General Virology 77, 1397-1402.[CrossRef] [Google Scholar]
  2. Armstrong, S. J., McInerney, T. L., McLain, L., Wahren, B., Hinkula, J., Levi, M. & Dimmock, N. J. (1996). Two neutralizing anti-V3 monoclonal antibodies act by affecting different functions of human immunodeficiency virus type 1.Journal of General Virology 77, 2931-2941.[CrossRef] [Google Scholar]
  3. Broliden, P.-A., von Gegerfelt, A., Clapham, P., Rosen, J., Fenyö, E.-M., Wahren, B. & Broliden, K. (1992). Identification of human neutralization-inducing regions of the human immunodeficiency virus type 1 envelope glycoproteins.Proceedings of the National Academy of Sciences, USA 89, 461-465.[CrossRef] [Google Scholar]
  4. Buratti, E., Tisminetzky, S. G., Scodeller, E. S. & Baralle, F. E. (1996). Conformational display of two neutralizing epitopes of HIV-1 gp41 in the flock house virus capsid protein.Journal of Immunological Methods 197, 7-18.[CrossRef] [Google Scholar]
  5. Buratti, E., McLain, L., Tisminetzky, S., Cleveland, S. M., Dimmock, N. J. & Baralle, F. E. (1998). The neutralizing antibody response against a conserved region of human immunodeficiency virus type 1 gp41 (amino acid residues 731–752) is uniquely directed against a conformational epitope.Journal of General Virology 79, 2709-2716. [Google Scholar]
  6. Burton, D. R., Pyati, J., Koduri, R., Sharp, S. J., Thornton, G. B., Parren, P. W. H. I., Sawyer, L. S. W., Hendry, R. M., Dunlop, N., Nara, P. L., Lamacchia, M., Garratty, E., Stiehm, E. R., Bryson, Y., Cao, Y., Moore, J. P., Ho, D. D. & Barbas, C. F.III (1994). Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody.Science 266, 1024-1027.[CrossRef] [Google Scholar]
  7. Chanh, T. C., Dreesman, G. R., Kanda, P., Linette, G. P., Sparrow, J. T., Ho, D. D. & Kennedy, R. C. (1986). Induction of anti-HIV neutralizing antibodies by synthetic peptides.EMBO Journal 5, 3065-3071. [Google Scholar]
  8. Cleveland, S. M., Buratti, E., Jones, T. D., North, P., Baralle, F., McLain, L., McInerney, T., Durrani, Z. & Dimmock, N. J. (2000). Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response.Virology 266, 66-78.[CrossRef] [Google Scholar]
  9. Conley, A. J., Kessler, J. A.II, Boots, L. J., Tung, J.-S., Arnold, B. A., Keller, P. M., Shaw, A. R. & Emini, E. A. (1994). Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody.Proceedings of the National Academy of Sciences, USA 91, 3348-3352.[CrossRef] [Google Scholar]
  10. Cordell, J., Moore, J. P., Dean, C. J., Klasse, P. J., Weiss, R. A. & McKeating, J. A. (1991). Rat monoclonal antibodies to nonoverlapping epitopes of human immunodeficiency virus type 1 gp120 block CD4 binding in vitro.Virology 185, 72-79.[CrossRef] [Google Scholar]
  11. Dalgleish, A. G., Chanh, T. C., Kennedy, R. C., Kanda, P., Clapham, P. R. & Weiss, R. A. (1988). Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide.Virology 165, 209-215.[CrossRef] [Google Scholar]
  12. Dalsgaard, K., Uttenthal, Å., Jones, T. D., Xu, F., Merryweather, A., Hamilton, W. D. O., Langeveld, J. P. M., Boshuizen, R. S., Kamstrup, S., Lomonossoff, G. P., Porta, C., Vela, C., Casal, J. I., Meloen, R. H. & Rodgers, P. B. (1997). Plant-derived vaccine protects target animals against a viral disease.Nature Biotechnology 15, 248-252.[CrossRef] [Google Scholar]
  13. Davis, D., Chaudhri, B., Stephens, D. M., Carne, C. A., Willers, C. & Lachmann, P. J. (1990). The immunodominance of epitopes within the transmembrane protein (gp41) of human immunodeficiency virus type 1 may be determined by the host’s previous exposure to similar epitopes on unrelated antigens.Journal of General Virology 71, 1975-1983.[CrossRef] [Google Scholar]
  14. Evans, D. J., McKeating, J., Meredith, J. M., Burke, K. L., Katrak, K., John, A., Ferguson, M., Minor, P. D., Weiss, R. A. & Almond, J. W. (1989). An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies.Nature 339, 385-388.[CrossRef] [Google Scholar]
  15. Goudsmit, J., Geelen, J., Keulen, W., Notermans, D., Kuiken, C., Ramautarsing, C., Smit, L., Koole, L., van Genderen, M., Buck, H., Sninsky, J. & Krone, W. (1990a). Characterization of the African HIV-1 isolate CBL-4 (RUT) by partial sequence analysis and virus neutralization with peptide antibody and antisense phosphate-methylated DNA.AIDS 4, 559-564.[CrossRef] [Google Scholar]
  16. Goudsmit, J., Meloen, R. H. & Brasseur, R. (1990b). Map of sequential B cell epitopes of the HIV-1 transmembrane protein using human antibodies as probe.Intervirology 31, 327-338. [Google Scholar]
  17. Jackson, N. A. C., Levi, M., Wahren, B. & Dimmock, N. J. (1999). Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions.Journal of General Virology 80, 225-236. [Google Scholar]
  18. Kalyan, N. K., Lee, S.-G., Wilhelm, J., Pisano, M. R., Hum, W.-T., Hsiao, C.-L., Davis, A. R., Eichberg, J. W., Robert-Guroff, M. & Hung, P. P. (1994). Immunogenicity of recombinant influenza virus haemagglutinin carrying peptides from the envelope protein of human immunodeficiency virus type 1.Vaccine 12, 753-760.[CrossRef] [Google Scholar]
  19. Kennedy, R. C., Henkel, R. D., Pauletti, D., Allan, J. S., Lee, T. H., Essex, M. & Dreesman, G. R. (1986). Antiserum to a synthetic peptide recognizes the HTLV-III envelope glycoprotein.Science 231, 1556-1559.[CrossRef] [Google Scholar]
  20. Klasse, P. J., McKeating, J. A., Schutten, M., Reitz, M. S.Jr & Robert-Guroff, M. (1993). An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env: Ala582→Thr) decreases viral neutralization by monoclonal antibodies to the CD4-binding site.Virology 196, 332-337.[CrossRef] [Google Scholar]
  21. Krause, R. M., Dimmock, N. J. & Morens, D. M. (1997). Summary of antibody workshop: the role of humoral immunity in the treatment and prevention of emerging and extant infectious diseases.Journal of Infectious Diseases 176, 549-559.[CrossRef] [Google Scholar]
  22. McInerney, T. L., McLain, L., Armstrong, S. J. & Dimmock, N. J. (1997). A human IgG1 (b12) specific for the CD4 binding site of HIV-1 neutralizes by inhibiting the virus fusion entry process, but b12 Fab neutralizes by inhibiting a postfusion event.Virology 233, 313-326.[CrossRef] [Google Scholar]
  23. McKeating, J. A., Thali, M., Furman, C., Karwowska, S., Gorny, M. K., Cordell, J., Zolla-Pazner, S., Sodroski, J. & Weiss, R. A. (1992). Amino acid residues of the human immunodeficiency virus type 1 gp120 critical for the binding of rat and human neutralizing antibodies that block the gp120–sCD4 interaction.Virology 190, 134-142.[CrossRef] [Google Scholar]
  24. McLain, L. & Dimmock, N. J. (1994). Single- and multi-hit kinetics of immunoglobulin G neutralization of human immunodeficiency virus type 1 by monoclonal antibodies.Journal of General Virology 75, 1457-1460.[CrossRef] [Google Scholar]
  25. McLain, L., Porta, C., Lomonossoff, G. P., Durrani, Z. & Dimmock, N. J. (1995). Human immunodeficiency virus type 1-neutralizing antibodies raised to a glycoprotein 41 peptide expressed on the surface of a plant virus.AIDS Research and Human Retroviruses 11, 327-334.[CrossRef] [Google Scholar]
  26. McLain, L., Durrani, Z., Wisniewski, L. A., Porta, C., Lomonossoff, G. P. & Dimmock, N. J. (1996a). A plant virus–HIV-1 chimera stimulates antibody that neutralizes HIV-1. In Vaccine 96, pp. 311-316. Edited by F. Brown, D. R. Burton, J. Collier, J. Mekalonos & E. Norrby. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  27. McLain, L., Durrani, Z., Wisniewski, L. A., Porta, C., Lomonossoff, G. P. & Dimmock, N. J. (1996b). Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus.Vaccine 14, 799-810.[CrossRef] [Google Scholar]
  28. Mondor, I., Ugolini, S. & Sattentau, Q. J. (1998). Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4 independent and gp120 dependent and requires cell surface heparans.Journal of Virology 72, 3623-3634. [Google Scholar]
  29. Muster, T., Steindl, F., Purtscher, M., Trkola, A., Klima, A., Himmler, G., Rüker, F. & Katinger, H. (1993). A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1.Journal of Virology 67, 6642-6647. [Google Scholar]
  30. Myers, G., Korber, B., Wain-Hobson, S., Smith, R. F. & Pavlakis, G. N. (editors) (1993).Human Retroviruses and AIDS, 1993: a Compilation and Analysis of Nucleic Acid and Amino Acid Sequences. Los Alamos, NM: Los Alamos National Laboratory.
  31. Newton, S. M. C., Joys, T. M., Anderson, S. A., Kennedy, R. C., Hovi, M. E. & Stocker, B. A. D. (1995). Expression and immunogenicity of an 18-residue epitope of HIV1 gp41 inserted in the flagellar protein of a Salmonella live vaccine.Research in Microbiology 146, 203-216.[CrossRef] [Google Scholar]
  32. Niedrig, M., Bröker, M., Walter, G., Stüber, W., Harthus, H.-P., Mehdi, S., Gelderblom, H. R. & Pauli, G. (1992). Murine monoclonal antibodies directed against the transmembrane protein gp41 of human immunodeficiency virus type 1 enhance its infectivity.Journal of General Virology 73, 951-954.[CrossRef] [Google Scholar]
  33. Pincus, S. H., Messer, K. G., Schwartz, D. H., Lewis, G. K., Graham, B. S., Blattner, W. A. & Fisher, G. (1993). Differences in the antibody response to human immunodeficiency virus-1 envelope glycoprotein (gp160) in infected laboratory workers and vaccinees.Journal of Clinical Investigation 91, 1987-1996.[CrossRef] [Google Scholar]
  34. Pincus, S. H., Messer, K. G. & Hu, S.-L. (1994). Effect of nonprotective vaccination on antibody response to subsequent human immunodeficiency virus infection.Journal of Clinical Investigation 93, 140-146.[CrossRef] [Google Scholar]
  35. Porta, C., Spall, V. E., Loveland, J., Johnson, J. E., Barker, P. J. & Lomonossoff, G. P. (1994). Development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides.Virology 202, 949-955.[CrossRef] [Google Scholar]
  36. 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., Ivanoff, L., Petteway, S. R., Pearson, M. L., Lautenberger, J. A., Papas, T. S., Ghrayeb, J., Chang, N. T., Gallo, R. C. & Wong-Staal, F. (1985). Complete nucleotide sequence of the AIDS virus, HTLV-III.Nature 313, 277-284.[CrossRef] [Google Scholar]
  37. Reitz, M. S.Jr, Wilson, C., Naugle, C., Gallo, R. C. & Robert-Guroff, M. (1988). Generation of a neutralization-resistant variant of HIV-1 is due to selection for a point mutation in the envelope gene.Cell 54, 57-63.[CrossRef] [Google Scholar]
  38. Sattentau, Q. J., Zolla-Pazner, S. & Poignard, P. (1995). Epitope exposure on functional, oligomeric HIV-1 gp41 molecules.Virology 206, 713-717.[CrossRef] [Google Scholar]
  39. Ugolini, S., Mondor, I., Parren, P. W. H. I., Burton, D. R., Tilley, S. A., Klasse, P. J. & Sattentau, Q. J. (1997). Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization.Journal of Experimental Medicine 186, 1287-1298.[CrossRef] [Google Scholar]
  40. Vella, C., Minor, P. D., Weller, I. V. D., Jenkins, O., Evans, D. & Almond, J. (1991). Recognition of poliovirus/HIV chimaeras by antisera from individuals with HIV infection.AIDS 5, 425-430.[CrossRef] [Google Scholar]
  41. Vella, C., Ferguson, M., Dunn, G., Meloen, R., Langedijk, H., Evans, D. & Minor, P. D. (1993). Characterization and primary structure of a human immunodeficiency virus type 1 (HIV-1) neutralization domain as presented by a poliovirus type 1/HIV-1 chimera.Journal of General Virology 74, 2603-2607.[CrossRef] [Google Scholar]
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Properties of a neutralizing antibody that recognizes a conformational form of epitope ERDRD in the gp41 C-terminal tail of human immunodeficiency virus type 1
J. Gen. Virol. 81, 1251 (2000); https://doi.org/10.1099/0022-1317-81-5-1251
/content/journal/jgv/10.1099/0022-1317-81-5-1251
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