HIV-1gp120V3区的结构特征及其生物学功能

研究表明HIV-1包膜蛋白gp120上的V3环在病毒结合到靶细胞的过程中起着重要的作用.这个区域中的几个氨基酸残基与gp120同辅受体的结合相关联.在HIV-1感染过程的早期,V3环在患者体内诱导针对HIV病毒的抗体应答,并被确定为主要中和决定簇.一些针对V3环的抗体具有广泛的中和活性.但是,V3环是HIV包膜蛋白的一个高变区,发生着广泛的变异.综述了V3环的结构特征和变异以及生物学功能,并对V3环的免疫反应进行了探讨.     

Predefined GPGRAFY-Epitope-Specific Monoclonal Antibodies with Different Activities for Recognizing Native HIV-1 gp120

A seven-amino acid epitope GPGRAFY at the tip of the V3 loop in HIV-1 gp120 is the principal neutralizing epitope, and a subset of anti-V3 antibodies specific for this epitope shows a broad range of neutralizing activity. GPGRAFY-epitope-specific neutralizing antibodies were produced using predefined GPGRAFY-epitope-specific peptides instead of a natural or recombinant gp120 bearing this epitope. All six monoclonal antibodies (mAbs) could recognize the GPGRAFY-epitope on peptides and two of the antibodies, 9D8 and 2D7, could recognize recombinant gp120 in enzymelinked immunosorkentassy (ELISA) assays. In the flow cytometry analysis, the mAbs 9D8 and 2D7 could bind to HIV-Env CHO-WT cells and the specific bindings could be inhibited by the GPGRAFY-epitope peptide, which suggests that these two mAbs could recognize the native envelope protein gp120 expressed on the cell membrane. However, in syncytium assays, none of the mAbs was capable of inhibiting HIV-Env-mediated cell membrane fusion. The different activities for recognizing native HIV-1 gp120 might be associated with different antibody affinities against the epitopes. The development of conformational mimics of the neutralization epitope in the gp120 V3 loop could elicit neutralizing mAbs with high affinity.