Marichannegowda Manukumar, Heredia Alonso, Wang Yin, Song Hongshuo
bioRxiv. 2024 Mar 13:2024.03.13.584899. doi: 10.1101/2024.03.13.584899.
HIV-1 is considered to become less susceptible to existing neutralizing antibodies over time. Our study on the virulent B (VB) HIV-1 identified genetic signatures responsible for immune escape from broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 glycan epitopes. We found that the absence of N295 and N332 glycans in the high mannose patch, which are crucial for neutralization by V3 glycan bNAbs and are typically conserved in subtype B HIV-1, is a notable feature in more than half of the VB variants. Neutralization assays confirmed that the loss of these two glycans in VB HIV-1 leads to escape from V3 glycan bNAbs. Additionally, all VB variants we investigated have an insertion in V2, contributing to immune escape from V1/V2 bNAbs PG9 and PG16. These findings suggest potential co-evolution of HIV-1 virulence and antigenicity, underscoring the need to monitor both the pathogenicity and neutralization susceptibility of newly emerged HIV-1 strains.
随着时间的推移，HIV-1被认为对现有的中和抗体越来越不敏感。我们对毒性B型（VB）HIV-1的研究确定了导致其从靶向V1/V2和V3聚糖表位的广泛中和抗体（bNAbs）中产生免疫逃逸的基因特征。我们发现，高甘露糖区域中N295和N332聚糖的缺失是超过一半的VB变体的一个显著特征，这两种聚糖对V3聚糖bNAbs的中和作用至关重要，并且在B亚型HIV-1中通常是保守的。中和试验证实，VB HIV-1中这两种聚糖的缺失导致其从V3聚糖bNAbs中逃逸。此外，我们研究的所有VB变体在V2中有一个插入，有助于其从V1/V2 bNAbs PG9和PG16中产生免疫逃逸。这些发现表明HIV-1毒力和抗原性可能共同进化，强调了监测新出现的HIV-1毒株的致病性和中和敏感性的必要性。
