Imaging early steps of HIV-1 infection and virus-host factor interactions
HIV-1 感染的早期成像和病毒-宿主因子相互作用
基本信息
- 批准号:10548587
- 负责人:
- 金额:$ 58.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-17 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:Amino AcidsAntiviral AgentsBindingBiochemicalBiochemistryBiological AssayBiophysicsCapsidCapsid ProteinsCell NucleusCell fusionCellsComplexConflict (Psychology)CytoplasmDNADNA IntegrationDataDyesElectron MicroscopyEventGenesGenetic TranscriptionGenomeHIVHIV-1ImageImaging DeviceImaging TechniquesImaging technologyIn VitroInfectionInnate Immune ResponseIntegraseIntegration Host FactorsKnowledgeLabelLightLocationMacromolecular ComplexesMapsMass Spectrum AnalysisMicroscopyModelingNuclearNuclear ImportNuclear PorePermeabilityProcessProteinsRecombinantsRegulationReportingReverse TranscriptionRibonucleoproteinsRoleSiteTechniquesTechnologyTravelTubeValidationViralVirusVisualizationbaseexperimental studyintegration siteknock-downlive cell imagingminimally invasivenovelnovel strategiesnovel virusnucleocytoplasmic transportrecruitstemstructural biologytranscriptional coactivator p75viral DNAviral RNAvirology
项目摘要
Key steps of early HIV-1 infection include reverse transcription, nuclear import of replication complexes and
transport to nuclear speckles followed by viral DNA integration into host genome. At some point before
integration, the capsid shell surrounding the viral ribonucleoprotein complex must disassemble (uncoat) to
release the viral pre-integration complexes. It is currently unclear where in the cell uncoating occurs and whether
the capsid (CA) protein is progressively or synchronously lost from the capsid shell, yet optimal core stability is
essential for evading the host innate immune responses and for nuclear import of functional viral complexes.
Highly divergent findings regarding HIV-1 uncoating have been reported by several groups based upon the
visualization of single virus uncoating in live cells. These conflicting results stem, in part, from the use of indirect
CA labeling approaches and lack of minimally invasive direct fluorescent labeling of HIV-1 capsid. We
hypothesize that HIV-1 uncoating is a multi-step process that involves permeabilization of the capsid shell in the
cytoplasm, remodeling at the nuclear pore, and loss of CA in the nucleus. We will use a novel minimally invasive
direct CA labeling strategy, which is based on site-directed incorporation of non-canonical amino acids and click-
labeling with an organic dye, to elucidate single HIV-1 core permeabilization and uncoating events resulting to
infection (Aim 1). Another gap in knowledge pertains to post-uncoating processes leading to HIV-1 integration
and sub-nuclear compartments where integration occurs. We hypothesize that the viral pre-integration complex
separates from the capsid shell and travels to the edge of a nuclear speckle where it engages the integrase-
binding host factor LEDGF/p75 for integration into host genome. We will employ a novel live-cell single viral DNA
visualization technology to track nuclear transport and productive integration of single viral complexes that
establish actively transcribing viral RNA foci (Aim 2). Finally, we will use a powerful panel of biochemical,
biophysical, structural biology, virology, and microscopy techniques to characterize a novel HIV-1 CA binding
host factor, RBM14, which we hypothesize to modulate pre-integration steps of infection after nuclear import
(Aim 3). These experiments are expected to elucidate the controversial HIV-1 uncoating process, reveal the
dynamic events leading to productive integration and sites of integration, as well as delineate the role of RBM14-
capsid interactions in early infection, thus informing novel antiviral strategies.
早期HIV-1感染的关键步骤包括逆转录、复制复合体的核输入和
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Mamuka Kvaratskhelia其他文献
Mamuka Kvaratskhelia的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Mamuka Kvaratskhelia', 18)}}的其他基金
Imaging early steps of HIV-1 infection and virus-host factor interactions
HIV-1 感染的早期成像和病毒-宿主因子相互作用
- 批准号:
10646359 - 财政年份:2022
- 资助金额:
$ 58.21万 - 项目类别:
Core B: Proteomics and Protein Analysis Core
核心 B:蛋白质组学和蛋白质分析核心
- 批准号:
8742037 - 财政年份:2014
- 资助金额:
$ 58.21万 - 项目类别:
Cellular Cofactors of Murine Leukemia Virus Integrase
鼠白血病病毒整合酶的细胞辅因子
- 批准号:
8709737 - 财政年份:2014
- 资助金额:
$ 58.21万 - 项目类别:
Cellular Cofactors of Murine Leukemia Virus Integrase
鼠白血病病毒整合酶的细胞辅因子
- 批准号:
8797297 - 财政年份:2014
- 资助金额:
$ 58.21万 - 项目类别:
Structural determinants for integrase pleiotropism in viral maturation
病毒成熟过程中整合酶多效性的结构决定因素
- 批准号:
10363022 - 财政年份:2012
- 资助金额:
$ 58.21万 - 项目类别:
相似海外基金
Development of a new generation of antiviral agents that are effective against drug-resistant viruses and prevent serious illness and sequelae.
开发新一代抗病毒药物,可有效对抗耐药病毒并预防严重疾病和后遗症。
- 批准号:
23K18186 - 财政年份:2023
- 资助金额:
$ 58.21万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
A versatile structure-based therapeutic platform for development of VHH-based antitoxin and antiviral agents
一个多功能的基于结构的治疗平台,用于开发基于 VHH 的抗毒素和抗病毒药物
- 批准号:
10560883 - 财政年份:2023
- 资助金额:
$ 58.21万 - 项目类别:
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
- 批准号:
10730692 - 财政年份:2021
- 资助金额:
$ 58.21万 - 项目类别:
Design and synthesis of nucleosides to develop antiviral agents and oligonucleotide therapeutics
设计和合成核苷以开发抗病毒药物和寡核苷酸疗法
- 批准号:
21K06459 - 财政年份:2021
- 资助金额:
$ 58.21万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
- 批准号:
10189880 - 财政年份:2021
- 资助金额:
$ 58.21万 - 项目类别:
Computer-aided identification and synthesis of novel broad-spectrum antiviral agents
新型广谱抗病毒药物的计算机辅助鉴定和合成
- 批准号:
2404261 - 财政年份:2020
- 资助金额:
$ 58.21万 - 项目类别:
Studentship
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10222540 - 财政年份:2020
- 资助金额:
$ 58.21万 - 项目类别:
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10669717 - 财政年份:2020
- 资助金额:
$ 58.21万 - 项目类别:
Association between sedentary lifestyle and liver cancer development in hepatitis C patients treated with direct-acting antiviral agents
接受直接抗病毒药物治疗的丙型肝炎患者久坐的生活方式与肝癌发展之间的关系
- 批准号:
20K10713 - 财政年份:2020
- 资助金额:
$ 58.21万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10174522 - 财政年份:2020
- 资助金额:
$ 58.21万 - 项目类别: