A primary concern of an antibody-based HIV-1 therapy is the virus' ability to rapidly escape antibody responses. Therefore, we investigated the relationships between antibody neutralization sensitivity, viral phenotype, and infectivity in 13 subtype C viruses using a HeLa transfectant-based assay. We observed that the seven tier 3 viruses exhibited higher infectivity than the tier 2 viruses, suggesting that higher neutralization resistance did not have a substantial entry cost. There was no relationship between neutralization resistance and susceptibility to entry inhibitors Maraviroc, PSC RANTES, or the fusion inhibitor T20, indicating that neutralization resistance may not alter these inhibitor target sites. By analyzing glycosylation patterns in 82 subtype C viruses, we found that the presence of an N-linked glycan motif at position N413 and its absence at N332 were the most important predictors of neutralization resistance. In a set of 200 subtype C viruses, tier 3 strains were more resistant than tier 2 or 1B viruses to several broadly neutralizing monoclonal antibodies targeting three different epitopes. This suggests that it is unlikely that resistance to antibodies targeting a single epitope drives overall resistance. In the context of an antibody-based intervention, highly resistant viruses with increased infectivity, circulating in the population, could hinder HIV-1 control since entry of tier 3 viruses is not always selected against. Therefore, for any long-term antibody-based intervention to be globally relevant, it must elicit responses that limit the occurrence of resistance.

中文翻译：

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与第 2 层病毒相比，HIV-1 C 亚型第 3 层病毒具有更高的传染性。

基于抗体的 HIV-1 疗法的一个主要问题是病毒快速逃避抗体反应的能力。因此，我们使用基于 HeLa 转染子的测定研究了 13 种 C 亚型病毒的抗体中和敏感性、病毒表型和感染性之间的关系。我们观察到七种三级病毒比二级病毒表现出更高的传染性，这表明更高的中和抗性没有大量的进入成本。中和抗性与进入抑制剂 Maraviroc、PSC RANTES 或融合抑制剂 T20 的敏感性之间没有关系，表明中和抗性可能不会改变这些抑制剂的靶位点。通过分析 82 种 C 亚型病毒的糖基化模式，我们发现 N413 位点存在 N-连接聚糖基序和 N332 位不存在是中和抗性的最重要预测因素。在一组 200 种 C 亚型病毒中，3 级毒株比 2 级或 1B 级病毒对针对三种不同表位的几种广泛中和的单克隆抗体具有更强的抵抗力。这表明对针对单个表位的抗体的抗性不太可能驱动整体抗性。在基于抗体的干预的背景下，在人群中传播的具有更高传染性的高抗性病毒可能会阻碍 HIV-1 的控制，因为并不总是针对第 3 级病毒的进入。因此，要使任何基于抗体的长期干预措施具有全球相关性，它必须引发限制耐药性发生的反应。