The V3 loop is accessible on the surface of most human immunodeficiency virus type 1 primary isolates and serves as a neutralization epitope
The V3 loop is accessible on the surface of most human immunodeficiency virus type 1 primary isolates and serves as a neutralization epitope
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DOI：
10.1128/jvi.78.5.2394-2404.2004
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Zolla-Pazner, S
中科院分区：
文献类型：
--
作者：
Gorny, MK;Revesz, K;Zolla-Pazner, S
针对人类免疫缺陷病毒1型（HIV - 1）gp120包膜糖蛋白V3环的抗体（Abs）最初被认为仅介导对T细胞系适应病毒的型特异性中和作用。然而，近期数据表明，交叉中和的V3抗体也存在，并且原代分离株可被抗V3单克隆抗体（MAbs）有效中和。然而，抗V3多克隆抗体和单克隆抗体的中和活性可能会因V3区域的抗原变异、完整病毒粒子表面V3暴露不足或抗体特异性而受到限制。为阐明这一问题，在荧光素酶试验中，对一组32种人源抗V3单克隆抗体进行筛选，以检测其对一种SF162假型病毒的中和能力。用一种V3融合蛋白（其V3区域模拟天然病毒的构象）筛选出的单克隆抗体比用V3肽筛选出的单克隆抗体效力显著更强。在单轮外周血单个核细胞试验中，进一步测试了7种单克隆抗体对13种B亚型病毒的中和活性。虽然观察到抗V3单克隆抗体对病毒的敏感性存在差异，但13种病毒中有12种可被一种或多种抗V3单克隆抗体中和。单克隆抗体与完整病毒粒子的结合与它和溶解的gp120的结合以及中和效力显著相关。这些结果表明，V3环在天然病毒包膜上是可及的，抗V3抗体的结合强度与中和效力相关，V3表位可能是共享的而非型特异性的，并且针对V3环的抗体，特别是那些靶向构象表位的抗体，能够介导对原代分离株的中和作用。
Antibodies (Abs) against the V3 loop of the human immunodeficiency virus type 1 gp120 envelope glycoprotein were initially considered to mediate only type-specific neutralization of T-cell-line-adapted viruses. However, recent data show that cross-neutralizing V3 Abs also exist, and primary isolates can be efficiently neutralized with anti-V3 monoclonal Abs (MAbs). The neutralizing activities of anti-V3 polyclonal Abs and MAN may, however, be limited due to antigenic variations of the V3 region, a lack of V3 exposure on the surface of intact virions, or Ab specificity. For clarification of this issue, a panel of 32 human anti-V3 MAbs were screened for neutralization of an SF162-pseudotyped virus in a luciferase assay. MAbs selected with a V3 fusion protein whose V3 region mimics the conformation of the native virus were significantly more potent than MAbs selected with V3 peptides. Seven MAbs were further tested for neutralizing activity against 13 clade B viruses in a single-round peripheral blood mononuclear cell assay. While there was a spectrum of virus sensitivities to the anti-V3 MAbs observed, 12 of the 13 viruses were neutralized by one or more of the anti-V3 MAbs. MAb binding to intact virions correlated significantly with binding to solubilized gp120s and with the potency of neutralization. These results demonstrate that the V3 loop is accessible on the native virus envelope, that the strength of binding of anti-V3 Abs correlates with the potency of neutralization, that V3 epitopes may be shared rather than type specific, and that Abs against the V3 loop, particularly those targeting conformational epitopes, can mediate the neutralization of primary isolates.