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. 1993 Mar;67(3):1612–1619. doi: 10.1128/jvi.67.3.1612-1619.1993

Autologous antibody response against the principal neutralizing domain of human immunodeficiency virus type 1 isolated from infected humans.

K Holmbäck 1, P Kusk 1, E F Hulgaard 1, T H Bugge 1, E Scheibel 1, B O Lindhardt 1
PMCID: PMC237532  PMID: 8437232

Abstract

High titers of neutralizing antibodies in human immunodeficiency virus type 1 (HIV-1) infection are directed primarily against the third hypervariable domain (V3) of the virion envelope glycoprotein gp120. This region has been designated the principal neutralizing domain of HIV-1. Because the frequency and significance of autologous V3 antibodies in natural infection are not fully clarified, we have cloned, sequenced, and expressed the V3 domain from virus of HIV-1-infected patients to test the autologous and heterologous V3 antibody response. The resulting recombinant Escherichia coli V3 fusion proteins reacted strongly with both autologous and heterologous patient antibodies in Western blots. Thirty-one different V3 fragments were cloned from 24 hemophiliac patients with different immunological and clinical statuses. Antibody reactivity against the autologous V3 fusion proteins was detected in all serum samples except one; moreover, all serum samples contained antibody reactivity against a vast majority of heterologous fusion proteins despite significant amino acid variability in V3. The results suggest that V3 antibodies are highly prevalent; further, we find no association between the stage of the HIV-1 infection and the presence of V3 antibodies.

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Selected References

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

  1. Albert J., Abrahamsson B., Nagy K., Aurelius E., Gaines H., Nyström G., Fenyö E. M. Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS. 1990 Feb;4(2):107–112. doi: 10.1097/00002030-199002000-00002. [DOI] [PubMed] [Google Scholar]
  2. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
  3. Boucher C. A., de Wolf F., Houweling J. T., Bakker M., Dekker J., Roos M. T., Coutinho R. A., van der Noordaa J., Goudsmit J. Antibody response to a synthetic peptide covering a LAV-1/HTLV-IIIB neutralization epitope and disease progression. AIDS. 1989 Feb;3(2):71–76. doi: 10.1097/00002030-198902000-00003. [DOI] [PubMed] [Google Scholar]
  4. Bressan G. M., Stanley K. K. pUEX, a bacterial expression vector related to pEX with universal host specificity. Nucleic Acids Res. 1987 Dec 10;15(23):10056–10056. doi: 10.1093/nar/15.23.10056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bugge T. H., Lindhardt B. O., Hansen L. L., Kusk P., Hulgaard E., Holmbäck K., Klasse P. J., Zeuthen J., Ulrich K. Analysis of a highly immunodominant epitope in the human immunodeficiency virus type 1 transmembrane glycoprotein, gp41, defined by a human monoclonal antibody. J Virol. 1990 Sep;64(9):4123–4129. doi: 10.1128/jvi.64.9.4123-4129.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clements G. J., Price-Jones M. J., Stephens P. E., Sutton C., Schulz T. F., Clapham P. R., McKeating J. A., McClure M. O., Thomson S., Marsh M. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? AIDS Res Hum Retroviruses. 1991 Jan;7(1):3–16. doi: 10.1089/aid.1991.7.3. [DOI] [PubMed] [Google Scholar]
  7. Doorbar J., Campbell D., Grand R. J., Gallimore P. H. Identification of the human papilloma virus-1a E4 gene products. EMBO J. 1986 Feb;5(2):355–362. doi: 10.1002/j.1460-2075.1986.tb04219.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Emini E. A., Nara P. L., Schleif W. A., Lewis J. A., Davide J. P., Lee D. R., Kessler J., Conley S., Matsushita S., Putney S. D. Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectivity for chimpanzees. J Virol. 1990 Aug;64(8):3674–3678. doi: 10.1128/jvi.64.8.3674-3678.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Emini E. A., Schleif W. A., Nunberg J. H., Conley A. J., Eda Y., Tokiyoshi S., Putney S. D., Matsushita S., Cobb K. E., Jett C. M. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature. 1992 Feb 20;355(6362):728–730. doi: 10.1038/355728a0. [DOI] [PubMed] [Google Scholar]
  10. Epstein L. G., Kuiken C., Blumberg B. M., Hartman S., Sharer L. R., Clement M., Goudsmit J. HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies. Virology. 1991 Feb;180(2):583–590. doi: 10.1016/0042-6822(91)90072-j. [DOI] [PubMed] [Google Scholar]
  11. Fahey J. L., Taylor J. M., Detels R., Hofmann B., Melmed R., Nishanian P., Giorgi J. V. The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. N Engl J Med. 1990 Jan 18;322(3):166–172. doi: 10.1056/NEJM199001183220305. [DOI] [PubMed] [Google Scholar]
  12. Girard M., Kieny M. P., Pinter A., Barre-Sinoussi F., Nara P., Kolbe H., Kusumi K., Chaput A., Reinhart T., Muchmore E. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542–546. doi: 10.1073/pnas.88.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gnann J. W., Jr, Nelson J. A., Oldstone M. B. Fine mapping of an immunodominant domain in the transmembrane glycoprotein of human immunodeficiency virus. J Virol. 1987 Aug;61(8):2639–2641. doi: 10.1128/jvi.61.8.2639-2641.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goudsmit J., Boucher C. A., Meloen R. H., Epstein L. G., Smit L., van der Hoek L., Bakker M. Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition. AIDS. 1988 Jun;2(3):157–164. [PubMed] [Google Scholar]
  15. Hoffman A. D., Banapour B., Levy J. A. Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions. Virology. 1985 Dec;147(2):326–335. doi: 10.1016/0042-6822(85)90135-7. [DOI] [PubMed] [Google Scholar]
  16. Hofmann B. AIDS immunology. HIV induced cellular immune deficiency. Dan Med Bull. 1991 Feb;38(1):53–67. [PubMed] [Google Scholar]
  17. 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]
  18. Klasse P. J., Pipkorn R., Blomberg J. Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5225–5229. doi: 10.1073/pnas.85.14.5225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koch C., Skjødt K., Laursen I. A simple immunoblotting method after separation of proteins in agarose gel. J Immunol Methods. 1985 Nov 28;84(1-2):271–278. doi: 10.1016/0022-1759(85)90434-x. [DOI] [PubMed] [Google Scholar]
  20. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Lifson J. D., Reyes G. R., McGrath M. S., Stein B. S., Engleman E. G. AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science. 1986 May 30;232(4754):1123–1127. doi: 10.1126/science.3010463. [DOI] [PubMed] [Google Scholar]
  23. Nara P. L., Smit L., Dunlop N., Hatch W., Merges M., Waters D., Kelliher J., Gallo R. C., Fischinger P. J., Goudsmit J. Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees. J Virol. 1990 Aug;64(8):3779–3791. doi: 10.1128/jvi.64.8.3779-3791.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Närvänen A., Korkolainen M., Kontio S., Suni J., Turtianen S., Partanen P., Soos J., Vaheri A., Huhtala M. L. Highly immunoreactive antigenic site in a hydrophobic domain of HIV-1 gp41 which remains undetectable with conventional immunochemical methods. AIDS. 1988 Apr;2(2):119–123. doi: 10.1097/00002030-198804000-00008. [DOI] [PubMed] [Google Scholar]
  25. Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Profy A. T., Salinas P. A., Eckler L. I., Dunlop N. M., Nara P. L., Putney S. D. Epitopes recognized by the neutralizing antibodies of an HIV-1-infected individual. J Immunol. 1990 Jun 15;144(12):4641–4647. [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. 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]
  30. Saag M. S., Hahn B. H., Gibbons J., Li Y., Parks E. S., Parks W. P., Shaw G. M. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  31. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  32. Scott C. F., Jr, Silver S., Profy A. T., Putney S. D., Langlois A., Weinhold K., Robinson J. E. Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8597–8601. doi: 10.1073/pnas.87.21.8597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Simmonds P., Balfe P., Ludlam C. A., Bishop J. O., Brown A. J. Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. J Virol. 1990 Dec;64(12):5840–5850. doi: 10.1128/jvi.64.12.5840-5850.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Wang J. J., Steel S., Wisniewolski R., Wang C. Y. Detection of antibodies to human T-lymphotropic virus type III by using a synthetic peptide of 21 amino acid residues corresponding to a highly antigenic segment of gp41 envelope protein. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6159–6163. doi: 10.1073/pnas.83.16.6159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Willumsen B. M., Christensen A., Hubbert N. L., Papageorge A. G., Lowy D. R. The p21 ras C-terminus is required for transformation and membrane association. Nature. 1984 Aug 16;310(5978):583–586. doi: 10.1038/310583a0. [DOI] [PubMed] [Google Scholar]
  37. Wolfs T. F., Zwart G., Bakker M., Valk M., Kuiken C. L., Goudsmit J. Naturally occurring mutations within HIV-1 V3 genomic RNA lead to antigenic variation dependent on a single amino acid substitution. Virology. 1991 Nov;185(1):195–205. doi: 10.1016/0042-6822(91)90767-6. [DOI] [PubMed] [Google Scholar]

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