Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, United States.
Bioinformatics. 2024 Mar 4;40(3). doi: 10.1093/bioinformatics/btae103.
Changing the course of the human immunodeficiency virus type I (HIV-1) pandemic is a high public health priority with approximately 39 million people currently living with HIV-1 (PLWH) and about 1.5 million new infections annually worldwide. Broadly neutralizing antibodies (bnAbs) typically target highly conserved sites on the HIV-1 envelope glycoproteins (Envs), which mediate viral entry, and block the infection of diverse HIV-1 strains. But different mechanisms of HIV-1 resistance to bnAbs prevent robust application of bnAbs for therapeutic and preventive interventions.
Here we report the development of a new database that provides data and computational tools to aid the discovery of resistant features and may assist in analysis of HIV-1 resistance to bnAbs. Bioinformatic tools allow identification of specific patterns in Env sequences of resistant strains and development of strategies to elucidate the mechanisms of HIV-1 escape; comparison of resistant and sensitive HIV-1 strains for each bnAb; identification of resistance and sensitivity signatures associated with specific bnAbs or groups of bnAbs; and visualization of antibody pairs on cross-sensitivity plots. The database has been designed with a particular focus on user-friendly and interactive interface. Our database is a valuable resource for the scientific community and provides opportunities to investigate patterns of HIV-1 resistance and to develop new approaches aimed to overcome HIV-1 resistance to bnAbs.
HIResist is freely available at https://hiresist.ahc.umn.edu/.
改变人类免疫缺陷病毒 I 型 (HIV-1) 大流行的进程是一项高度优先的公共卫生重点,目前全球约有 3900 万人感染 HIV-1(PLWH),每年约有 150 万新感染病例。广泛中和抗体 (bnAbs) 通常针对 HIV-1 包膜糖蛋白 (Envs) 上高度保守的位点,这些位点介导病毒进入并阻止多种 HIV-1 株的感染。但是,HIV-1 对 bnAbs 的不同耐药机制阻止了 bnAbs 在治疗和预防干预中的广泛应用。
在这里,我们报告了一个新数据库的开发,该数据库提供数据和计算工具,以帮助发现耐药特征,并可能有助于分析 HIV-1 对 bnAbs 的耐药性。生物信息学工具允许识别耐药株 Env 序列中的特定模式,并制定策略以阐明 HIV-1 逃逸的机制;比较每种 bnAb 的耐药和敏感 HIV-1 株;鉴定与特定 bnAbs 或 bnAbs 组相关的耐药和敏感特征;以及在交叉敏感性图上可视化抗体对。该数据库的设计特别注重用户友好和交互式界面。我们的数据库是科学界的宝贵资源,为研究 HIV-1 耐药模式和开发旨在克服 HIV-1 对 bnAbs 耐药性的新方法提供了机会。
HIResist 可在 https://hiresist.ahc.umn.edu/ 免费获得。