Antibody-mediated enhancement of human immunodeficiency virus type 1 infectivity is determined by the structure of gp120 and depends on modulation of the gp120-CCR5 interaction

被引:25
作者
Guillon, C
Schutten, M
Boers, PHM
Gruters, RA
Osterhaus, ADME
机构
[1] Erasmus Univ, Dept Virol, NL-3015 GE Rotterdam, Netherlands
[2] Ecole Normale Super Lyon, UMR 2142, CNRS, BioMerieux, F-69364 Lyon, France
关键词
D O I
10.1128/JVI.76.6.2827-2834.2002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In this study, we characterized the viral determinants of coreceptor usage in relation to susceptibility to antibody-mediated neutralization or enhancement of infectivity by using chimeras of three highly related human immunodeficiency virus type I (HIV-1) isolates of different phenotypes. We found that the V3 region was the main determinant of antibody-mediated enhancement and coreceptor specificity but that the overall structure of gp120 was also important for these properties. Constructs susceptible to antibody-mediated enhancement preferentially use CCR5 as a coreceptor, in contrast to constructs that were neutralized or not affected. Using monoclonal antibodies directed against CD4 or CCR5, we were able to show that antibody-mediated enhancement was CD4 dependent. Altogether, our results suggest that the modulation of the interaction of gp120 with CCR5 is the mechanism underlying antibody-mediated enhancement of HIV-1 infectivity.
引用
收藏
页码:2827 / 2834
页数:8
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