HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEUTRALIZATION IS DETERMINED BY EPITOPE EXPOSURE ON THE GP120 OLIGOMER

被引:315
作者
SATTENTAU, QJ [1 ]
MOORE, JP [1 ]
机构
[1] NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016
关键词
D O I
10.1084/jem.182.1.185
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The major target of the neutralizing antibody response to infection by the human immunodeficiency virus type 1 (HIV-1) is the outer envelope glycoprotein, gp120. The spectrum of HIV-1 neutralization specificity is currently represented by monoclonal antibodies (mAbs) that can be divided broadly into five groups. We have studied the binding of these mAbs to functional oligomeric and soluble monomeric gp120 derived from the molecular clone of a cell line-adapted isolate of HIV-1, and compared these binding properties with virus neutralization. Binding of all mAbs except those reactive with the V3 loop was much weaker to oligomeric than to monomeric gp120. This reduction in binding to oligomeric gp120 was determined mostly by a slower relative rate of association, although the dissociation rate also had some influence on relative variation in mAb affinity. Virus neutralization correlated broadly with mAb binding to the oligomeric rather than to the monomeric form of gp120, and neutralization potency was related to the estimated association rate. Thus, with the exception of the hypervariable V3 loop, regions of HIV-1 gp120 with the potential to induce a neutralization response are likely to be poorly presented for antibody recognition on the surface of cell line-adapted virions.
引用
收藏
页码:185 / 196
页数:12
相关论文
共 66 条
  • [1] BONHABIB DC, 1994, J VIROL, V68, P6006
  • [2] FUSION FROM WITHOUT DIRECTED BY HUMAN-IMMUNODEFICIENCY-VIRUS PARTICLES
    CLAVEL, F
    CHARNEAU, P
    [J]. JOURNAL OF VIROLOGY, 1994, 68 (02) : 1179 - 1185
  • [3] EFFECTS OF MUTATIONS IN HYPERCONSERVED REGIONS OF THE EXTRACELLULAR GLYCOPROTEIN OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 ON RECEPTOR-BINDING
    CORDONNIER, A
    RIVIERE, Y
    MONTAGNIER, L
    EMERMAN, M
    [J]. JOURNAL OF VIROLOGY, 1989, 63 (10) : 4464 - 4468
  • [4] THE CD4 (T4) ANTIGEN IS AN ESSENTIAL COMPONENT OF THE RECEPTOR FOR THE AIDS RETROVIRUS
    DALGLEISH, AG
    BEVERLEY, PCL
    CLAPHAM, PR
    CRAWFORD, DH
    GREAVES, MF
    WEISS, RA
    [J]. NATURE, 1984, 312 (5996) : 763 - 767
  • [5] HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 AND SIMIAN IMMUNODEFICIENCY VIRUS ENV PROTEINS POSSESS A FUNCTIONALLY CONSERVED ASSEMBLY DOMAIN
    DOMS, RW
    EARL, PL
    CHAKRABARTI, S
    MOSS, B
    [J]. JOURNAL OF VIROLOGY, 1990, 64 (07) : 3537 - 3540
  • [6] HIV-1 NEUTRALIZING MONOCLONAL-ANTIBODIES INDUCED BY A SYNTHETIC PEPTIDE
    DURDA, PJ
    BACHELER, L
    CLAPHAM, P
    JENOSKI, AM
    LEECE, B
    MATTHEWS, TJ
    MCKNIGHT, A
    POMERANTZ, R
    RAYNER, M
    WEINHOLD, KJ
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1990, 6 (09) : 1115 - 1123
  • [7] NATIVE OLIGOMERIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN ELICITS DIVERSE MONOCLONAL-ANTIBODY REACTIVITIES
    EARL, PL
    BRODER, CC
    LONG, D
    LEE, SA
    PETERSON, J
    CHAKRABARTI, S
    DOMS, RW
    MOSS, B
    [J]. JOURNAL OF VIROLOGY, 1994, 68 (05) : 3015 - 3026
  • [8] OLIGOMERIC STRUCTURE OF THE HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN
    EARL, PL
    DOMS, RW
    MOSS, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (02) : 648 - 652
  • [9] A MOLECULAR CLONE OF HTLV-III WITH BIOLOGICAL-ACTIVITY
    FISHER, AG
    COLLALTI, E
    RATNER, L
    GALLO, RC
    WONGSTAAL, F
    [J]. NATURE, 1985, 316 (6025) : 262 - 265
  • [10] MONOCLONAL-ANTIBODIES THAT NEUTRALIZE HIV-1 VIRIONS AND INHIBIT SYNCYTIUM FORMATION BY INFECTED-CELLS
    FUNG, MSC
    SUN, C
    SUN, NC
    CHANG, NT
    CHANG, TW
    [J]. BIO-TECHNOLOGY, 1987, 5 (09): : 940 - &