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首页> 美国卫生研究院文献>PLoS Clinical Trials >Cross-Neutralizing Antibodies in HIV-1 Individuals Infected by Subtypes B, F1, C or the B/Bbr Variant in Relation to the Genetics and Biochemical Characteristics of the env Gene
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Cross-Neutralizing Antibodies in HIV-1 Individuals Infected by Subtypes B, F1, C or the B/Bbr Variant in Relation to the Genetics and Biochemical Characteristics of the env Gene

机译：B型，F1，C型或B / Bbr亚型感染的HIV-1个体的交叉中和抗体与env基因的遗传学和生化特性有关

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Various HIV-1 env genetic and biochemical features impact the elicitation of cross-reactive neutralizing antibodies in natural infections. Thus, we aimed to investigate cross-neutralizing antibodies in individuals infected with HIV-1 env subtypes B, F1, C or the B/Bbr variant as well as env characteristics. Therefore, plasma samples from Brazilian chronically HIV-1 infected individuals were submitted to the TZM-bl neutralization assay. We also analyzed putative N-glycosylation sites (PNGLs) and the size of gp120 variable domains in the context of HIV-1 subtypes prevalent in Brazil. We observed a greater breadth and potency of the anti-Env neutralizing response in individuals infected with the F1 or B HIV-1 subtypes compared with the C subtype and the variant B/Bbr. We observed greater V1 B/Bbr and smaller V4 F1 than those of other subtypes (p<0.005), however neither was there a correlation verified between the variable region length and neutralization potency, nor between PNLG and HIV-1 subtypes. The enrichment of W at top of V3 loop in weak neutralizing response viruses and the P in viruses with higher neutralization susceptibility was statistically significant (p = 0.013). Some other signatures sites were associated to HIV-1 subtype-specific F1 and B/Bbr samples might influence in the distinct neutralizing response. These results indicate that a single amino acid substitution may lead to a distinct conformational exposure or load in the association domain of the trimer of gp120 and interfere with the induction power of the neutralizing response, which affects the sensitivity of the neutralizing antibody and has significant implications for vaccine design.
机译：HIV-1 env的各种遗传和生化特征都会影响自然感染中交叉反应中和抗体的产生。因此，我们旨在研究感染HIV-1 env B，F1，C或B / Bbr变异亚型的个体中的交叉中和抗体以及env特性。因此，将来自巴西慢性HIV-1感染者的血浆样品进行TZM-bl中和试验。我们还分析了假定的N-糖基化位点（PNGLs）和在巴西流行的HIV-1亚型情况下gp120可变域的大小。我们观察到，与C亚型和变异B / Bbr相比，在感染F1或B HIV-1亚型的个体中，抗Env中和反应的广度和效力更大。与其他亚型相比，我们观察到更大的V1 B / Bbr和更小的V4 F1（p <0.005），但是在可变区长度和中和力之间，PNLG和HIV-1亚型之间均未发现相关性。弱中和反应病毒中V3环顶部的W富集，中和敏感性较高的病毒中P的富集具有统计学意义（p = 0.013）。其他一些特征位点与HIV-1亚型特异性F1和B / Bbr样品有关，可能会影响独特的中和反应。这些结果表明，单个氨基酸取代可能会导致gp120三聚体的缔合域发生明显的构象暴露或负载，并干扰中和反应的诱导能力，从而影响中和抗体的敏感性，并具有重要意义。用于疫苗设计。

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