Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations
Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations
复制标题
DOI：
10.1038/s41467-019-10899-2
复制
发表时间：
2019-07-01
影响因子：
16.6
通讯作者：
Saunders, Kevin O.
中科院分区：
文献类型：
--
作者：
Han, Qifeng;Jones, Julia A.;Saunders, Kevin O.
HIV-1包膜（Env）是中和抗体的靶标，以开放或封闭构象存在于病毒体表面。难以中和的病毒（第2层）以封闭构象表达Env，对广泛中和抗体（bnAb）具有抗原性，但对第三可变区（V3）抗体不具有抗原性。在这里，我们表明，由Env疫苗接种引起的选择V3猕猴抗体可以中和26%的标准化病毒组中的其他2级HIV-1分离株。V3抗体仅以其开放构象结合Env。因此，2级病毒上的Envs采样V3环不在其闭合构象位置的状态。包膜第二可变区长度、糖基化位点和V3氨基酸是中和敏感性的标志。本研究确定，暴露V3的Env的开放构象存在于中和抗性病毒体的子集上，因此，2级HIV-1的中和并不总是表明bnAb诱导。
The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a closed conformation antigenic for broadly neutralizing antibodies (bnAbs) but not for third variable region (V3) antibodies. Here we show that select V3 macaque antibodies elicited by Env vaccination can neutralize 26% of otherwise tier 2 HIV-1 isolates in standardized virus panels. The V3 antibodies only bound to Env in its open conformation. Thus, Envs on tier 2 viruses sample a state where the V3 loop is not in its closed conformation position. Envelope second variable region length, glycosylation sites and V3 amino acids were signatures of neutralization sensitivity. This study determined that open conformations of Env with V3 exposed are present on a subset of otherwise neutralization-resistant virions, therefore neutralization of tier 2 HIV-1 does not always indicate bnAb induction.