Characterization of RHA:RT interactions in HIV-1 reverse transcription
Characterization of RHA:RT interactions in HIV-1 reverse transcription
批准号:
10403061
负责人:
Kathleen A. Boris-Lawrie
金额:
$26.25万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-05-01 至 2024-04-30
关键词:
AddressAffectAffinityAntiviral TherapyBindingBiological AssayBiophysicsCause of DeathCellsComplementComplementary DNAComplexCryoelectron MicroscopyDNA biosynthesisDataDevelopmentDockingDouble-Stranded RNADouble-Stranded RNA Binding DomainDrug resistanceElementsEnsureEquilibriumEukaryotaEventEvolutionGelGenetic RecombinationGenetic VariationGenomeGenomic SegmentGoalsHIV-1Immune responseInfectionInvestigationLengthLocationMapsMediatingModelingMolecularMolecular BiologyMolecular VirologyMutationNucleotidesOpen Reading FramesPolymeraseProkaryotic CellsRNARNA HelicaseRNA SequencesRNA chemical synthesisRNA helicase ARNA-Binding ProteinsRNA-Directed DNA PolymeraseRegulatory ElementResolutionRetroviridaeReverse TranscriptionRibonucleic Acid Regulatory SequencesRoleStructureTranscription ProcessVaccinesVariantViral GenomeVirionVirusVirus ReplicationWorkbasegenomic RNAhelicaseimprovedinsightmonomermutantnovelpreferencepressurereconstructionrecruitresistant strainstructural biologytargeted treatmenttranscriptome sequencingviral DNAviral RNAviral fitnessviral genomics
中文摘要
项目总结
英文摘要
Project Summary
HIV-1 infection is one of the leading causes of death globally. The urgent need for the
development of new antiviral therapies arises from the lack of vaccine and emerging of drug-
resistant strains. HIV-1 reverse transcriptase (RT) is an error-prone polymerase responsible for
the emergence of notorious drug resistant mutants. Due to the low processivity, RT pauses on
certain RNA sequences/structures and the pausing is correlated with high mutation and
recombination rate. The mechanism that maintains fidelity relatively high in the RNA regulatory
regions but error-prone in open reading frames during reverse transcription is poorly understood.
Host helicase DHX9/RNA helicase A (RHA) is recruited into virions and promotes processivity of
RT. Preliminary data suggest dynamic RT: RHA interactions during reverse transcription and
reveal that RHA improves RT’s fidelity on structured regulatory RNA regions. The overall goal of
this proposal is to establish the structural basis for RHA-mediated RT fidelity modulation during
reverse transcription. Aim 1 will characterize the RHA-dependent fidelity enhanced hotspots in
the viral genomic RNA by sequencing the cDNA synthesized in the absence and presence of host
RHA. Aim 2 will characterize the RT:RHA interactions by cryo-EM, and validate by cell-based
assays. The proposed studies will offer insights into the mechanism of the host helicase mediated
modulation of RT pausing and fidelity at various locations of the genomic RNA during reverse
transcription, and provide structural basis for the development of novel antiviral therapies.
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会议论文
HIV-1 cap epigenetic modification
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批准号:10866730
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项目类别:
-
资助金额:$57.24万
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财政年份:2023
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负责人:Kathleen A. Boris-Lawrie
-
依托单位:
Characterization of RHA:RT interactions in HIV-1 reverse transcription
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批准号:10614580
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项目类别:
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资助金额:$19.52万
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财政年份:2022
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
The Center for HIV RNA Studies (CRNA)
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批准号:8512891
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项目类别:
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资助金额:$21.71万
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财政年份:2012
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
Translational Control of Retroviral Unspliced mRNA
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批准号:7039375
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项目类别:
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资助金额:$20.35万
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财政年份:2006
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
Translational Control of Retroviral Unspliced mRNA
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批准号:7339629
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项目类别:
-
资助金额:$19.31万
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财政年份:2006
-
负责人:Kathleen A. Boris-Lawrie
-
依托单位:
Translational Control of Retroviral Unspliced mRNA
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批准号:7544521
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项目类别:
-
资助金额:$19.31万
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财政年份:2006
-
负责人:Kathleen A. Boris-Lawrie
-
依托单位:
Translational Control of Retroviral Unspliced mRNA
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批准号:7996196
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项目类别:
-
资助金额:$19.31万
-
财政年份:2006
-
负责人:Kathleen A. Boris-Lawrie
-
依托单位:
Translational Control of Retroviral Unspliced mRNA
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批准号:7176238
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项目类别:
-
资助金额:$19.31万
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财政年份:2006
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
Retrovirus Models of Cellular Post-transcriptional Gene Expression
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批准号:8376222
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项目类别:
-
资助金额:$20.0万
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财政年份:2003
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
Retrovirus Models of Cellular Post-transcriptional Gene Expression
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批准号:8079529
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项目类别:
-
资助金额:$20.75万
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财政年份:2003
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负责人:Kathleen A. Boris-Lawrie
-
依托单位:
Retrovirus Models of Cellular Post-transcriptional Gene Expression
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批准号:8299996
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项目类别:
-
资助金额:$20.12万
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财政年份:2003
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负责人:Kathleen A. Boris-Lawrie
-
依托单位:
Retrovirus Models of Cellular Post-transcriptional Gene Expression
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批准号:7383667
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项目类别:
-
资助金额:$14.69万
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财政年份:2003
-
负责人:Kathleen A. Boris-Lawrie
-
依托单位:
Retrovirus Models of Cellular Post-transcriptional Gene Expression
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批准号:7876676
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项目类别:
-
资助金额:$20.34万
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财政年份:2003
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
INDUCTION OF ANTIVIRAL IMMUNITY
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批准号:6364001
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项目类别:
-
资助金额:$4.03万
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财政年份:2000
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
INDUCTION OF ANTIVIRAL IMMUNITY
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批准号:6531180
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项目类别:
-
资助金额:$4.03万
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财政年份:2000
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
INDUCTION OF ANTIVIRAL IMMUNITY
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批准号:6053592
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项目类别:
-
资助金额:$3.8万
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财政年份:2000
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
HIV STRUCTURAL GENE VECTORS--LIVE ATTENUATED HIV VACCINE
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批准号:6021286
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项目类别:
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资助金额:$21.9万
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财政年份:1999
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
HIV/SIV STRUCTURAL GENE VECTORS AS A LIVE HIV VACCINE
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批准号:2799594
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项目类别:
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资助金额:$3.65万
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财政年份:1999
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
HIV STRUCTURAL GENE VECTORS--LIVE-ATTENUATED HIV VACCINE
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批准号:6170687
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项目类别:
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资助金额:$21.9万
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财政年份:1999
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
RNA TRAFFICKING IN SIMPLIFIED HIV1 DERIVATIVES
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批准号:6170004
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项目类别:
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资助金额:$10.32万
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财政年份:1997
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负责人:Kathleen A. Boris-Lawrie
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依托单位:
海外基金