Genetic signatures in the highly virulent subtype B human immunodeficiency virus-1 conferring resistance to broadly neutralizing antibodies

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-07 DOI:10.1016/j.isci.2025.112847

Manukumar Honnayakanahalli Marichannegowda , Georgina Agyekum , Cinthya Zelaya Aparicio , Alonso Heredia , Yin Wang , Hongshuo Song

{"title":"Genetic signatures in the highly virulent subtype B human immunodeficiency virus-1 conferring resistance to broadly neutralizing antibodies","authors":"Manukumar Honnayakanahalli Marichannegowda , Georgina Agyekum , Cinthya Zelaya Aparicio , Alonso Heredia , Yin Wang , Hongshuo Song","doi":"10.1016/j.isci.2025.112847","DOIUrl":null,"url":null,"abstract":"<div><div>HIV-1 is considered to become less sensitive to existing neutralizing antibodies over time. Our study on virulent B (VB) HIV-1 identified genetic signatures responsible for immune escape from broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 epitopes. We found that the absence of the 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 have an insertion in V2, contributing to escape from V1/V2 bNAbs PG9 and PG16. These findings demonstrate that the VB strains have unique genetic and neutralization characteristics compared to other subtype B strains. The evolutionary origin of these distinctive features remains to be determined.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112847"},"PeriodicalIF":4.6000,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225011083","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

HIV-1 is considered to become less sensitive to existing neutralizing antibodies over time. Our study on virulent B (VB) HIV-1 identified genetic signatures responsible for immune escape from broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 epitopes. We found that the absence of the 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 have an insertion in V2, contributing to escape from V1/V2 bNAbs PG9 and PG16. These findings demonstrate that the VB strains have unique genetic and neutralization characteristics compared to other subtype B strains. The evolutionary origin of these distinctive features remains to be determined.

查看原文本刊更多论文

高毒力乙型人类免疫缺陷病毒-1亚型的遗传特征赋予对广泛中和抗体的抗性

HIV-1被认为随着时间的推移对现有的中和抗体变得不那么敏感。我们对强毒性B (VB) HIV-1的研究发现了针对V1/V2和V3表位的广泛中和抗体（bNAbs）免疫逃逸的遗传特征。我们发现，高甘露糖贴片中N295和N332聚糖的缺失是超过一半的VB变体的显著特征，而N295和N332聚糖对于V3聚糖bNAbs的中和至关重要，并且通常在B亚型HIV-1中保守。中和实验证实，VB HIV-1中这两种聚糖的缺失导致V3聚糖bnab的逃逸。此外，所有的VB变体在V2中都有一个插入，有助于逃避V1/V2的bNAbs PG9和PG16。这些结果表明，与其他B亚型菌株相比，VB菌株具有独特的遗传和中和特性。这些独特特征的进化起源仍有待确定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.