Home LiteratureArticle Details
PMID: 1378510 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells.

Journal of virology ·Vol. 66 ·No. 8 ·1992-08-00 ·Pages 4784-93

Moore JP, Sattentau QJ, Klasse PJ, Burkly LC

Abstract

The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we show that, in contrast to the CD4 domain 1 MAb 6H10, 5A8 and its Fab fragment do not block soluble CD4 (sCD4) binding to virions, whereas they do inhibit sCD4-induced exposure of cryptic epitopes on gp41 and dissociation of gp120 from virions. Two other MAbs, OKT4 and L120, which are reactive with domains 3 and 4 of CD4, have little or no effect on HIV-1 infection, syncytium formation, or sCD4-induced conformational changes in the envelope glycoproteins. The mechanisms of action of 5A8 and 6H10 can be further distinguished in syncytium inhibition assays: 6H10 blocks competitively, while 5A8 does not. We opine that 5A8 blocks HIV-1 infection and fusion by interfering with conformational changes in gp120/gp41 and/or CD4 that are necessary for virus-cell fusion.

MeSH Terms
Animals Antibodies, Monoclonal Antigen-Antibody Complex CD4 Antigens/immunology,metabolism Epitopes/immunology Giant Cells/immunology HIV-1/immunology,pathogenicity,physiology Humans Immunoglobulin Fab Fragments/immunology Mice Protein Conformation T-Lymphocyte Subsets/immunology,microbiology Viral Envelope Proteins/immunology,metabolism Virulence/immunology
Chemicals
Antibodies, Monoclonal Antigen-Antibody Complex CD4 Antigens Epitopes Immunoglobulin Fab Fragments Viral Envelope Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Moore J P
Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
Sattentau Q J
Klasse P J
Burkly L C
References (38)
38 references, click to expand
  1. Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization.
    J Virol. 1991 Feb;65(2):852-60 PMID: 1898972
  2. Initial stages of HIV-1 envelope glycoprotein-mediated cell fusion monitored by a new assay based on redistribution of fluorescent dyes.
    AIDS Res Hum Retroviruses. 1991 Oct;7(10):799-805 PMID: 1742075
  3. Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4616-20 PMID: 2052546
  4. Human immunodeficiency virus envelope glycoprotein/CD4-mediated fusion of nonprimate cells with human cells.
    J Virol. 1990 May;64(5):2149-56 PMID: 2109100
  5. Dissociation of gp120 from HIV-1 virions induced by soluble CD4.
    Science. 1990 Nov 23;250(4984):1139-42 PMID: 2251501
  6. Morphometric analysis of recombinant soluble CD4-mediated release of the envelope glycoprotein gp120 from HIV-1.
    AIDS Res Hum Retroviruses. 1990 Oct;6(10):1209-12 PMID: 2252640
  7. HIV requires multiple gp120 molecules for CD4-mediated infection.
    Nature. 1990 Jul 19;346(6281):277-9 PMID: 2374593
  8. 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):2937-44 PMID: 2428879
  9. Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells.
    Nature. 1989 Jan 26;337(6205):368-70 PMID: 2536142
  10. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain.
    Cell. 1986 Nov 7;47(3):333-48 PMID: 3094962
  11. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1.
    Science. 1987 Sep 11;237(4820):1351-5 PMID: 3629244
  12. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.
    Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7 PMID: 6096719
  13. Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4.
    J Virol. 1992 Jun;66(6):3531-7 PMID: 1583722
  14. Thermodynamic and kinetic analysis of sCD4 binding to HIV-1 virions and of gp120 dissociation.
    AIDS Res Hum Retroviruses. 1992 Apr;8(4):443-50 PMID: 1599754
  15. Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding.
    J Exp Med. 1990 Oct 1;172(4):1233-42 PMID: 1698911
  16. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding.
    J Exp Med. 1991 Aug 1;174(2):407-15 PMID: 1713252
  17. Kinetics of soluble CD4 binding to cells expressing human immunodeficiency virus type 1 envelope glycoprotein.
    J Virol. 1992 Jan;66(1):132-8 PMID: 1727475
  18. 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):235-43 PMID: 1727487
  19. 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):5007-12 PMID: 1870209
  20. Receptor-mediated activation of immunodeficiency viruses in viral fusion.
    Science. 1991 May 31;252(5010):1322-3 PMID: 1925547
  21. Synthetic peptides allow discrimination of structural features of CD4(81-92) important for HIV-1 infection versus HIV-1-induced syncytium formation.
    AIDS Res Hum Retroviruses. 1991 Jun;7(6):521-7 PMID: 1931230
  22. 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):2189-93 PMID: 2006155
  23. A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site.
    Cell. 1990 Mar 9;60(5):747-54 PMID: 2107024
  24. Simple methods for monitoring HIV-1 and HIV-2 gp120 binding to soluble CD4 by enzyme-linked immunosorbent assay: HIV-2 has a 25-fold lower affinity than HIV-1 for soluble CD4.
    AIDS. 1990 Apr;4(4):297-305 PMID: 2190604
  25. Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding.
    J Exp Med. 1990 Oct 1;172(4):1143-50 PMID: 2212945
  26. Enhancement of SIV infection with soluble receptor molecules.
    Science. 1990 Mar 2;247(4946):1084-8 PMID: 2309120
  27. HIV: early virus-cell interactions.
    J Acquir Immune Defic Syndr. 1990;3(10):965-74 PMID: 2398460
  28. 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):975-85 PMID: 2441877
  29. Structural analysis of the human immunodeficiency virus-binding domain of CD4. Epitope mapping with site-directed mutants and anti-idiotypes.
    J Exp Med. 1989 Oct 1;170(4):1319-34 PMID: 2477490
  30. 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):382-5 PMID: 3001934
  31. pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane.
    Cell. 1987 Jun 5;49(5):659-68 PMID: 3107838
  32. Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism.
    EMBO J. 1988 Feb;7(2):513-8 PMID: 3259178
  33. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV.
    Nature. 1984 Dec 20-1985 Jan 2;312(5996):767-8 PMID: 6083454
  34. Kinetics of the HIV-CD4 interactions and virus-cell fusion.
    AIDS. 1992 Mar;6(3):325-7 PMID: 1567578
  35. Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by Simian immunodeficiency virus.
    Virology. 1991 Apr;181(2):703-15 PMID: 1673040
  36. A region in domain 1 of CD4 distinct from the primary gp120 binding site is involved in HIV infection and virus-mediated fusion.
    J Biol Chem. 1991 Mar 25;266(9):5942-8 PMID: 1706342
  37. Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies.
    J Virol. 1991 Sep;65(9):4832-8 PMID: 1714520
  38. 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):1133-40 PMID: 1995942
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.8.4784-4793.1992
Published
1992-08-00
Pages
4784-93
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC241306
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.66.8.4784-4793.1992 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2