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人类Ⅰ型免疫缺陷病毒(human immunodeficiency class I, HIV-1)包膜蛋白gp41的近膜端外部区(membrane proximal external region, MPER)在HIV-1的各个分化株之间相当保守,这暗示MPER区对于病毒的生存和侵染均具有十分重要的作用.目前研究表明,两个靶向HIV-1且具有最广泛中和活性的单抗2F5和4E10,都特异地识别该区域,进而有效地抑制包膜蛋白介导的病毒膜融合过程.我们先前的研究表明,4E10抗体表位的抗原性和免疫原性会随着gp41融合核心区域的结构调整而发生显著的改变,提示在gp41蛋白的MPER区与融合核心区之间很有可能存在某种联系,并与gp41介导的膜融合过程相关.本研究利用各种不同的gp41融合核心区衍生多肽,检测了4E10表位多肽(D4E10P)与它们之间的反应性.其中,具有gp41蛋白核心区N-trimer结构的多肽(N-trimer-6HB)显示出很强的结合活性.进一步对N-trimer-6HB多肽进行噬菌体文库筛选,发现4E10表位上一个短的模体序列(WF)很有可能对gp41的N-trimer和MPER区之间的相互作用发挥了至关重要的作用,导致MPER区以潜在的方式参与病毒包膜和靶细胞膜间的融合过程.
The membrane proximal external region (MPER) of the human immunodeficiency class I (HIV-1) envelope protein gp41 is fairly conserved among all HIV-1 isolates, suggesting that MPER Region plays a very important role in the survival and infection of the virus.At present, studies have shown that two monoclonal antibodies 2F5 and 4E10 that target HIV-1 and have the most extensive neutralizing activity all specifically recognize this region and thus effectively Inhibit the envelope protein-mediated viral membrane fusion process.Our previous studies showed that antigenicity and immunogenicity of 4E10 epitopes changed significantly with the structural adjustment of gp41 fusion core region, suggesting that the gp41 protein It is possible that there is some connection between the MPER region and the fusion core region and is related to the gp41-mediated membrane fusion process.In this study, a variety of gp41 fusion core region-derived peptides were used to detect the 4E10 epitope polypeptide (D4E10P) And their reactivity, in which the N-trimer structure-bearing polypeptide (N-trimer-6HB) having the core region of gp41 protein shows strong binding activity.Furthermore, phage library screening of N-trimer- A short motif sequence (WF) on the 4E10 epitope is likely to play a crucial role in the interaction between the N-trimer and MPER regions of gp41, resulting in a potentially involved MPER region in the viral envelope and Target cell membrane fusion process.