• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Nov 1993; 67(11): 6642–6647.
PMCID: PMC238102

A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1.

Abstract

Vaccination against human immunodeficiency virus type 1 (HIV-1) requires an immunogen which will elicit a protective immunity against viruses that show a high degree of genetic polymorphism. Therefore, the identification of neutralizing epitopes which are shared by many strains would be useful. In previous studies, we established a human monoclonal antibody (2F5) that neutralizes a variety of laboratory strains and clinical isolates of HIV-1. In the present report, we define the amino acid sequence Glu-Leu-Asp-Lys-Trp-Ala (ELDKWA) on the ectodomain of gp41 as the epitope recognized by this antibody. The sequence was found to be conserved in 72% of otherwise highly variable HIV-1 isolates. Escape mutants were not detected in cells infected with HIV-1 isolates MN and RF in the presence of antibody 2F5. Since sequence variability of neutralizing epitopes is considered to be a major obstacle to HIV-1 vaccine development, the conserved B-cell epitope described here is a promising candidate for inclusion in a vaccine against AIDS.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Albert J, Abrahamsson B, Nagy K, Aurelius E, Gaines H, Nyström G, Fenyö EM. 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. [PubMed]
  • Broliden PA, von Gegerfelt A, Clapham P, Rosen J, Fenyö EM, Wahren B, Broliden K. Identification of human neutralization-inducing regions of the human immunodeficiency virus type 1 envelope glycoproteins. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):461–465. [PMC free article] [PubMed]
  • Cao J, Bergeron L, Helseth E, Thali M, Repke H, Sodroski J. Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. J Virol. 1993 May;67(5):2747–2755. [PMC free article] [PubMed]
  • Chaffee S, Leeds JM, Matthews TJ, Weinhold KJ, Skinner M, Bolognesi DP, Hershfield MS. Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines. J Exp Med. 1988 Aug 1;168(2):605–621. [PMC free article] [PubMed]
  • Chanh TC, Dreesman GR, Kanda P, Linette GP, Sparrow JT, Ho DD, Kennedy RC. Induction of anti-HIV neutralizing antibodies by synthetic peptides. EMBO J. 1986 Nov;5(11):3065–3071. [PMC free article] [PubMed]
  • Clavel F, Hoggan MD, Willey RL, Strebel K, Martin MA, Repaske R. Genetic recombination of human immunodeficiency virus. J Virol. 1989 Mar;63(3):1455–1459. [PMC free article] [PubMed]
  • Evans DJ, McKeating J, Meredith JM, Burke KL, Katrak K, John A, Ferguson M, Minor PD, Weiss RA, Almond JW. An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature. 1989 Jun 1;339(6223):385–340. [PubMed]
  • Goodrich DW, Duesberg PH. Retroviral recombination during reverse transcription. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2052–2056. [PMC free article] [PubMed]
  • Harada S, Koyanagi Y, Nakashima H, Kobayashi N, Yamamoto N. Tumor promoter, TPA, enhances replication of HTLV-III/LAV. Virology. 1986 Oct 30;154(2):249–258. [PubMed]
  • Inoue M, Hoxie JA, Reddy MV, Srinivasan A, Reddy EP. Mechanisms associated with the generation of biologically active human immunodeficiency virus type 1 particles from defective proviruses. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2278–2282. [PMC free article] [PubMed]
  • Javaherian K, Langlois AJ, LaRosa GJ, Profy AT, Bolognesi DP, Herlihy WC, Putney SD, Matthews TJ. Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1. Science. 1990 Dec 14;250(4987):1590–1593. [PubMed]
  • Kion TA, Hoffmann GW. Anti-HIV and anti-anti-MHC antibodies in alloimmune and autoimmune mice. Science. 1991 Sep 6;253(5024):1138–1140. [PubMed]
  • LaRosa GJ, Davide JP, Weinhold K, Waterbury JA, Profy AT, Lewis JA, Langlois AJ, Dreesman GR, Boswell RN, Shadduck P, et al. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. [PubMed]
  • Looney DJ, Fisher AG, Putney SD, Rusche JR, Redfield RR, Burke DS, Gallo RC, Wong-Staal F. Type-restricted neutralization of molecular clones of human immunodeficiency virus. Science. 1988 Jul 15;241(4863):357–359. [PubMed]
  • Masuda T, Matsushita S, Kuroda MJ, Kannagi M, Takatsuki K, Harada S. Generation of neutralization-resistant HIV-1 in vitro due to amino acid interchanges of third hypervariable env region. J Immunol. 1990 Nov 15;145(10):3240–3246. [PubMed]
  • McKeating JA, Gow J, Goudsmit J, Pearl LH, Mulder C, Weiss RA. Characterization of HIV-1 neutralization escape mutants. AIDS. 1989 Dec;3(12):777–784. [PubMed]
  • Nara PL, Smit L, Dunlop N, Hatch W, Merges M, Waters D, Kelliher J, Gallo RC, Fischinger PJ, 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. [PMC free article] [PubMed]
  • Nixon DF, Broliden K, Ogg G, Broliden PA. Cellular and humoral antigenic epitopes in HIV and SIV. Immunology. 1992 Aug;76(4):515–534. [PMC free article] [PubMed]
  • Palker TJ, Clark ME, Langlois AJ, Matthews TJ, Weinhold KJ, Randall RR, Bolognesi DP, Haynes BF. 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. [PMC free article] [PubMed]
  • Reitz MS, Jr, Wilson C, Naugle C, Gallo RC, Robert-Guroff M. Generation of a neutralization-resistant variant of HIV-1 is due to selection for a point mutation in the envelope gene. Cell. 1988 Jul 1;54(1):57–63. [PubMed]
  • Robert-Guroff M, Reitz MS, Jr, Robey WG, Gallo RC. In vitro generation of an HTLV-III variant by neutralizing antibody. J Immunol. 1986 Nov 15;137(10):3306–3309. [PubMed]
  • Roberts JD, Bebenek K, Kunkel TA. The accuracy of reverse transcriptase from HIV-1. Science. 1988 Nov 25;242(4882):1171–1173. [PubMed]
  • Robinson WE, Jr, Gorny MK, Xu JY, Mitchell WM, Zolla-Pazner S. Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro. J Virol. 1991 Aug;65(8):4169–4176. [PMC free article] [PubMed]
  • Robinson WE, Jr, Kawamura T, Gorny MK, Lake D, Xu JY, Matsumoto Y, Sugano T, Masuho Y, Mitchell WM, Hersh E, et al. Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3185–3189. [PMC free article] [PubMed]
  • Scott JK, Smith GP. Searching for peptide ligands with an epitope library. Science. 1990 Jul 27;249(4967):386–390. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Vanini S, Longhi R, Lazzarin A, Vigo E, Siccardi AG, Viale G. Discrete regions of HIV-1 gp41 defined by syncytia-inhibiting affinity-purified human antibodies. AIDS. 1993 Feb;7(2):167–174. [PubMed]
  • Wong-Staal F, Shaw GM, Hahn BH, Salahuddin SZ, Popovic M, Markham P, Redfield R, Gallo RC. Genomic diversity of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Aug 23;229(4715):759–762. [PubMed]
  • Zagury D, Bernard J, Cheynier R, Desportes I, Leonard R, Fouchard M, Reveil B, Ittele D, Lurhuma Z, Mbayo K, et al. A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS. Nature. 1988 Apr 21;332(6166):728–731. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...