1型人类免疫缺陷病毒感染性的抗体介导增强作用由gp120的结构决定，并取决于gp120与CCR5相互作用的调节。
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.
作者信息
Guillon Christophe, Schutten Martin, Boers Patrick H M, Gruters Rob A, Osterhaus Albert D M E
机构信息
Department of Virology, Erasmus University Rotterdam, 3015 GE Rotterdam, The Netherlands.
出版信息
J Virol. 2002 Mar;76(6):2827-34. doi: 10.1128/jvi.76.6.2827-2834.2002.
Abstract
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 1 (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.
摘要
在本研究中，我们通过使用三种不同表型的高度相关的人类免疫缺陷病毒1型（HIV-1）分离株的嵌合体，来确定共受体使用的病毒决定因素与抗体介导的中和作用或感染性增强易感性之间的关系。我们发现，V3区域是抗体介导的增强作用和共受体特异性的主要决定因素，但gp120的整体结构对这些特性也很重要。与被中和或未受影响的构建体相比，易受抗体介导增强作用影响的构建体优先使用CCR5作为共受体。使用针对CD4或CCR5的单克隆抗体，我们能够证明抗体介导的增强作用是CD4依赖性的。总之，我们的结果表明，gp120与CCR5相互作用的调节是抗体介导HIV-1感染性增强的潜在机制。
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