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首页> 外文期刊>AIDS Research and Human Retroviruses >HLA Homology within the C5 Domain Promotes Peptide Binding by HIV Type 1 gp120
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HLA Homology within the C5 Domain Promotes Peptide Binding by HIV Type 1 gp120

机译：C5域内的HLA同源性可促进HIV 1型gp120的肽结合

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摘要

The mechanisms by which HIV-1 induces chronic pathogenic immune activation associated with disease progression remain unclear despite many years of AIDS research. One proposal suggests that sequence and structural mimicry between gp120 and HLA may endow HIV with the capacity to arouse alloreactive and autoimmune responses within the susceptible host, fueling disease progression in a manner similar to graft-versus-host disease (GVHD). Both gp120 and HLA share a common functional interaction with CD4 but also demonstrate peptide binding properties. Here we report the conserved nature of this feature across HIV-1 envelopes, the crucial role of the HLA homologous C5 region for peptide interactions, and the elimination of this property through specific antibody targeting. Given that the C5 domain mimics a HLA activation domain and the reported clinical benefits associated with nonneutralizing antibodies against this region, targeting the C5 domain may have use as a therapeutic vaccine to protect against disease progression.
机译：尽管进行了多年的艾滋病研究，HIV-1诱导与疾病进展相关的慢性病原体免疫激活的机制仍不清楚。一项提议表明，gp120和HLA之间的序列和结构模拟可以赋予HIV在易感宿主内激发同种反应和自身免疫反应的能力，从而以类似于移植物抗宿主病（GVHD）的方式助长疾病的进展。 gp120和HLA均与CD4共享共同的功能相互作用，但也显示出肽结合特性。在这里，我们报告了跨HIV-1包膜的该功能的保守性质，HLA同源C5区域对于肽相互作用的关键作用，以及通过特异性抗体靶向消除了此特性。考虑到C5结构域模仿了HLA激活结构域，并且报道了与针对该区域的非中和抗体相关的临床益处，靶向C5结构域可用作预防疾病进展的治疗性疫苗。

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