Structural basis of the HIV-1 PBS-segment mediated RHA recruitment during assembly to bolster virus infectivity

HIV-1 PBS 片段在组装过程中介导的 RHA 募集以增强病毒感染性的结构基础

• 批准号: 9271533
• 负责人: Xiao Heng
• 金额: $ 31.54万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9271533
• 关键词: 5' Untranslated Regions; Address; Adopted; Affect; Antiviral Agents; Attenuated; Binding; Binding Sites; Biological; Biological Assay; Biophysics; Cause of Death; Cells; Complex; Data; Deuterium; Dimerization; Double-Stranded RNA Binding Domain; Goals; HIV; HIV-1; Hybrids; Infection; Integration Host Factors; Knowledge; Label; Laboratories; Maps; Mediating; Modeling; Molecular; Molecular Conformation; Mutation; Nuclear Magnetic Resonance; Nucleocapsid; Nucleocapsid Proteins; Parents; Point Mutation; Premature Mortality; Proteins; RNA; RNA helicase A; RNA-Binding Proteins; Recruitment Activity; Reporting; Resistance development; Resolution; Reverse Transcription; Roentgen Rays; Role; Signal Transduction; Structural Models; Structure; Testing; Transcription Initiation; Transfer RNA; Variant; Viral; Virion; Virus; Virus Assembly; Virus Diseases; Virus Replication; base; biophysical model; dimer; drug development; experimental study; genomic RNA; in vitro Assay; innovation; particle; prevent; stem; virus host interaction

Project Summary RNA Helicase A (RHA) is one of the cellular factors recruited into HIV-1 particles during virus assembly. The reduced infectivity of RHA-deficient virions demonstrates that the RHA molecules co-assembled with gRNA exert a continuous impact in early infection. However, it remains unclear how host RHA is specifically recruited during virus assembly, and how it supports the infectivity of progeny virions. Our laboratory has recently reported that the recruitment of RHA is mediated by the direct interactions between RHA and the PBS-segment of the viral genomic RNA during assembly. In addition, our preliminary studies indicate that the specific RHA:PBS-segment interaction may coordinate proper tRNA placement on the PBS-segment to initiate reverse transcription. We propose to employ an innovative integrated NMR/SAXS approach, in combination with cell-based functional assays, to determine the structural basis of the PBS-segment mediated recruitment of RHA during virus assembly, and to investigate the role of RHA during the early stage of viral replication.

项目摘要 RNA解旋酶A（RHA）是在HIV-1感染过程中募集到HIV-1颗粒中的细胞因子之一。 病毒组装RHA缺陷型病毒粒子的感染性降低表明， 与gRNA共组装的RHA分子在早期感染中发挥持续影响。 然而，目前还不清楚宿主RHA在病毒感染期间是如何特异性募集的。 组装，以及它如何支持子代病毒体的感染性。本实验室 最近报道RHA的募集是通过直接相互作用介导的， RHA和病毒基因组RNA的PBS片段之间的相互作用。在 此外，我们的初步研究表明，特定的RHA：PBS-片段相互作用 可以协调PBS节段上的适当tRNA位置，以启动逆转录酶， 转录。我们建议采用创新的综合NMR/SAXS方法， 结合基于细胞的功能测定，以确定细胞的结构基础。 PBS片段介导的RHA在病毒组装过程中的募集，并研究 RHA在病毒复制早期的作用。