MULTIFACETED CONSEQUENCES OF ANTI-GP41 MONOCLONAL-ANTIBODY 2F5 BINDING TO HIV TYPE-1 VIRIONS

被引：18

作者：

NEURATH, AR

STRICK, N

LIN, K

JIANG, S

机构：

[1] Lindsley F. Kimball Research Institute of the New York Blood Center, New York, New York 10021

来源：

AIDS RESEARCH AND HUMAN RETROVIRUSES | 1995年 / 11卷 / 06期

关键词：

D O I：

10.1089/aid.1995.11.687

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

A human monoclonal antibody (MAb) (2F5) neutralizing a variety of laboratory strains and clinical isolates of the human immunodeficiency virus type 1 (HIV-1) and binding to an epitope of the envelope glycoprotein gp41 encompassing the amino acid sequence ELDKWA has been described (Muster T et al., J Virol 1993;67:6642-6647). It was suggested that an immunogen eliciting virus-neutralizing antibodies having a specificity similar to that of MAb 2F5 should be considered as a component of HIV-1 vaccines,Efforts in this direction would benefit from understanding the mechanism whereby MAb 2F5 neutralizes the infectivity of HIV-1, The segment of gp41 encompassing residues ELDKWA has so far not been directly implicated in initiation of infection by HIV-1, suggesting that MAb 2F5 might affect other sites on HIV-1 envelope glycoproteins playing a role in virus entry into target cells, We provide here evidence that MAb 2F5 binding to HIV-1 virus particles decreases the accessibility or conformation of the gp41 fusion domain and of gp120 domains, including the binding site for the CD4 cell receptor, These apparently indirect consequences of MAb 2F5 binding to HIV-1 are likely to account for or contribute to the virus-neutralizing activity of this MAb.

引用

页码：687 / 696

页数：10

共 56 条

[11] Broliden P.-A., von Gegerfelt A., Clapham P., Rosen J., Fenyo E.M., Wahren B., Broliden K., Identification of human neutralization-inducing regions of the human immunodeficiency virus type 1 envelope glycoproteins, Proc Natl Acad Sci, 89, pp. 461-465, (1992)
[12] Chanh T.C., Dreesman G.R., Kanda P., Linette G.P., Sparrow J.T., Ho D.D., Kennedy R.C., Induction of anti-HIV neutralizing antibodies by synthetic peptides, EMBO J, 5, pp. 3065-3071, (1986)
[13] 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., An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies, Nature, 339, pp. 385-388, (1989)
[14] Buchacher A., Predl R., Strutzenberger K., Steinfellner W., Trkola A., Purtscher M., Gruber G., Tauer C., Steindl F., Jungbauer A., Katinger H., Generation of human monoclonal antibodies against HIV-1 proteins
[15] electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte inunortalization, AIDS Res Hum Retroviruses, 10, pp. 359-369, (1994)
[16] Muster T., Steindl F., Purtscher M., Trkola A., Klima A., Himmler G., Ruker F., Katinger H., A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1, J Virol, 67, pp. 6642-6647, (1993)
[17] Muster T., Guinea R., Trkola A., Purtscher M., Klima A., Steindl F., Palese P., Katinger H., Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS, J Virol, 68, pp. 4031-4034, (1994)
[18] Conley A.J., Kessler J.A., Boots U., Tung J.-S., Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody, Proc Natl Acad Sci, 91, pp. 3348-3352, (1994)
[19] Moore J.P., Simple methods for monitoring HIV-1 and HIV-2 gp 120 binding to soluble CD4 by enzyme-linked immunosorbent assay: HIV-2 has a 25-fold lower affinity than HIV-1 for soluble CD4, AIDS, 4, pp. 297-305, (1990)
[20] Moore J.P., McKeating J.A., Jones I.M., Stephens P.E., Clements G., Thomson S., Weiss R.A., Characterization of recombinant gp120 and gpl60 from HIV-1: Binding to monoclonal antibodies and soluble CD4, AIDS, 4, pp. 307-315, (1990)

← 1 2 3 4 5 6 →