Jackson N A, Levi M, Wahren B, Dimmock N J
J Gen Virol. 1999 Jan;80 ( Pt 1):225-236. doi: 10.1099/0022-1317-80-1-225.
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.
仅描述了两种病毒中和肽微抗体（MicroAbs），对其作用模式了解甚少。本报告涉及一种由单克隆抗体F58（IgG1）重链的第三个互补决定区衍生而来的17个氨基酸的环化微抗体，它在人免疫缺陷病毒1型（HIV-1）的gp120包膜蛋白的V3环中识别与单克隆抗体相同的最小表位。该微抗体能够结合并中和游离病毒颗粒。按质量计算，其效率比F58 IgG高5倍，其摩尔中和率仅低32倍。还研究了该微抗体的中和机制。在病毒与靶细胞C8166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%）。中和后的病毒附着于HIV-1的主要受体CD4。微抗体部分抑制了病毒粒子与细胞的融合，而F58 IgG已被证明能显著抑制融合。因此，微抗体的中和作用似乎至少部分是由融合抑制介导的。在第5或6位酪氨酸被缺失或替换为苯丙氨酸的对照肽没有显示出抗病毒活性，这证明了微抗体与病毒粒子相互作用的特异性。因此，微抗体的作用似乎类似于免疫球蛋白。数据还表明，V3环上的微抗体/单克隆抗体F58表位不参与病毒与CD4的附着，但在早期感染的后续事件中是必需的。
