Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions
Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions
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DOI：
10.1099/0022-1317-80-1-225
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发表时间：
1999-01-01
影响因子：
3.8
通讯作者：
Dimmock, NJ
中科院分区：
文献类型：
--
作者：
Jackson, NAC;Levi, M;Dimmock, NJ
只有两种病毒中和肽微抗体（MicroAbs）已被描述，很少有人知道他们的行动模式。本文报道了一种由单克隆抗体F58（IgG 1）重链第三互补决定区衍生的17个氨基酸环化的抗人免疫缺陷病毒（HIV-1）单克隆抗体，它识别HIV-1包膜蛋白gp 120 V3环上的最小抗原决定簇。它在质量方面比F58 IgG有效多达5倍，并且其在摩尔基础上的中和率仅低32倍。同时还研究了该抗体的中和机理。在病毒与靶C8166细胞的附着没有任何显著减少的情况下，发生了高水平的中和（99%）。中和病毒附着于HIV-1主要受体CD 4。病毒粒子与细胞的融合被MicroAb部分抑制，而F58 IgG已显示出显著抑制融合。因此，MicroAb的中和作用似乎至少部分是通过抑制融合来介导的。对照肽，其中5或6位的酪氨酸被删除或改变为苯丙氨酸，没有显示出抗病毒活性，证明了MicroAb与病毒粒子相互作用的特异性。因此，似乎MicroAb的作用类似于免疫球蛋白。数据还显示，V3环上的MicroAb/MAb F58表位不参与病毒与CD 4的附着，但在早期感染的后续事件中是必需的。
Only two virus-neutralizing peptide microantibodies (MicroAbs) have been described and little is known about their mode of action. This report concerns a 17 amino acid cyclized MicroAb, derived from the third complementarity-determining region of the heavy chain of MAb F58 (IgG1), that recognizes the same minimum epitope in the V3 loop of the gp120 envelope protein of human immunodeficiency virus type 1 (HIV-1) as the MAb, The MicroAb was able to bind to and neutralize free virus particles. It was up to 5-fold more efficient in mass terms than F58 IgG and its neutralization rate on a molar basis was only 32-fold lower. The mechanism of neutralization of the MicroAb was also investigated. A high level of neutralization (99%) occurred without any significant decrease in attachment of virus to target C8166 cells. Neutralized virus attached to CD4, the HIV-1 primary receptor. Fusion of virions to cells was partially inhibited by the MicroAb, whereas F58 IgG has been shown to inhibit fusion significantly. Thus, neutralization by the MicroAb appears to be mediated, at least in part, by inhibition of fusion. Control peptides, in which the tyrosine at position 5 or 6 was deleted or changed to phenylalanine, showed no antiviral activity, attesting to the specificity of interaction of the MicroAb with the virion. It therefore appears that the MicroAb acts like an immunoglobulin. The data also show that the MicroAb/MAb F58 epitope on the V3 loop is not involved in attachment of virus to CD4 but is required for subsequent events in early infection.