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

J P Moore, Q J Sattentau, P J Klasse, L C Burkly, J P Moore, Q J Sattentau, P J Klasse, L C Burkly

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.

References

    1. J Virol. 1991 Feb;65(2):852-60
    1. AIDS Res Hum Retroviruses. 1991 Oct;7(10):799-805
    1. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4616-20
    1. J Virol. 1990 May;64(5):2149-56
    1. Science. 1990 Nov 23;250(4984):1139-42
    1. AIDS Res Hum Retroviruses. 1990 Oct;6(10):1209-12
    1. Nature. 1990 Jul 19;346(6281):277-9
    1. J Immunol. 1986 Nov 1;137(9):2937-44
    1. Nature. 1989 Jan 26;337(6205):368-70
    1. Cell. 1986 Nov 7;47(3):333-48
    1. Science. 1987 Sep 11;237(4820):1351-5
    1. Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7
    1. J Virol. 1992 Jun;66(6):3531-7
    1. AIDS Res Hum Retroviruses. 1992 Apr;8(4):443-50
    1. J Exp Med. 1990 Oct 1;172(4):1233-42
    1. J Exp Med. 1991 Aug 1;174(2):407-15
    1. J Virol. 1992 Jan;66(1):132-8
    1. J Virol. 1992 Jan;66(1):235-43
    1. J Virol. 1991 Sep;65(9):5007-12
    1. Science. 1991 May 31;252(5010):1322-3
    1. AIDS Res Hum Retroviruses. 1991 Jun;7(6):521-7
    1. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2189-93
    1. Cell. 1990 Mar 9;60(5):747-54
    1. AIDS. 1990 Apr;4(4):297-305
    1. J Exp Med. 1990 Oct 1;172(4):1143-50
    1. Science. 1990 Mar 2;247(4946):1084-8
    1. J Acquir Immune Defic Syndr. 1990;3(10):965-74
    1. Cell. 1987 Sep 11;50(6):975-85
    1. J Exp Med. 1989 Oct 1;170(4):1319-34
    1. Science. 1986 Jan 24;231(4736):382-5
    1. Cell. 1987 Jun 5;49(5):659-68
    1. EMBO J. 1988 Feb;7(2):513-8
    1. Nature. 1984 Dec 20-1985 Jan 2;312(5996):767-8
    1. AIDS. 1992 Mar;6(3):325-7
    1. Virology. 1991 Apr;181(2):703-15
    1. J Biol Chem. 1991 Mar 25;266(9):5942-8
    1. J Virol. 1991 Sep;65(9):4832-8
    1. J Virol. 1991 Mar;65(3):1133-40

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren