Regulation of the Epstein-Barr Virus Lytic Switch
Epstein-Barr 病毒裂解开关的调节
基本信息
- 批准号:10643950
- 负责人:
- 金额:$ 50.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-06 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAdultAntigensArchitectureAuxinsB-LymphocytesBZLF1 geneBindingBinding SitesCRISPR screenCell CompartmentationCell NucleusCellsChIP-seqChromatin Conformation Capture and SequencingChromatin LoopClustered Regularly Interspaced Short Palindromic RepeatsComplexCuesDNA Polymerase IIEBV-associated diseaseEngineeringEpigenetic ProcessEpitheliumEpstein-Barr Virus latencyGene ExpressionGene Expression RegulationGenetic TranscriptionGenomeHairy LeukoplakiaHuman GenomeHuman Herpesvirus 4Immediate-Early GenesImmune EvasionImmune responseImmunoglobulinsInfectionInfectious MononucleosisIntegration Host FactorsKnowledgeLearningLocationLymphomaLyticLytic PhaseLytic VirusMalignant NeoplasmsMalignant neoplasm of nasopharynxMapsMediatorMemory B-LymphocyteMethylationMolecular ConformationNasopharynx CarcinomaOral cavityPRDM1 genePathway interactionsPhosphorylationPhysiologicalProto-Oncogene Proteins c-mycRNARegulationRepressionResolutionRoleSalivaSeriesStomach CarcinomaStructureSystemTherapeuticTonsilTranscription Factor AP-1Transcriptional RegulationViralViral GenomeViral ProteinsVirionWithdrawalXenograft procedureantagonistcohesincrosslinkds-DNAgenome-widein vivoinsightlytic replicationmalignant stomach neoplasmnovel therapeutic interventionplasma cell differentiationprogramspromoterrelease factorresponsesingle moleculetranscription factortransmission processtumorigenesisviral genomics
项目摘要
Abstract
Epstein-Barr virus (EBV) establishes lifelong infection in 95% of adults worldwide. EBV
causes infectious mononucleosis, lymphomas, nasopharyngeal and gastric cancer, and oral
hairy leukoplakia. EBV is transmitted between hosts through saliva, from which it translocates
across the oral cavity and tonsillar epithelium to reach the B-cell compartment. Upon B-cell
infection, the ~170 kilobase linear double-stranded DNA (dsDNA) EBV genome is delivered to
the nucleus. EBV then uses a series of latency programs to navigate the B-cell compartment,
and colonize the memory B-cell compartment. Ultimately, to spread between cells and to the
tonsillar epithelium for transfer to a new host, EBV must undergo lytic replication, in which
nearly 80 viral proteins are expressed and infectious virion are produced. Lytic replication is
increasingly implicated in oncogenesis. Yet, much remains to be learned about how the viral
lytic switch is controlled. We therefore used a human genome-wide CRISPR/Cas9 screen to
identify host factors that control the viral lytic switch. Our analyses a network of host factors that
repress lytic reactivation, centered on the transcription factor MYC, including cohesins, FACT,
STAGA, and Mediator. Depletion of MYC or factors important for MYC expression, reactivated
the lytic cycle, including in Burkitt xenografts. MYC bound the EBV genome origin of lytic
replication and suppressed its looping to the lytic cycle initiator BZLF1 promoter. Our central
hypothesis is that the MYC:MAX control the EBV lytic switch through regulation of viral genome
loop extrusion. Our Aims are to (1) Define key MYC roles in regulation of oriLyt loop extrusion to
control the EBV lytic switch; (2) Define MYC-gated cohesin roles in regulation of oriLyt loop
extrusion in EBV lytic switch control (3) Define MYC-gated CTCF roles in regulation of oriLyt
loop extrusion to control the EBV lytic switch. Collectively, these studies are expected to identify
how EBV subverts host DNA loop extrusion pathways to control the viral lytic switch.
Our studies may therefore support strategies to develop rational lytic induction therapeutic
therapies for EBV-associated diseases.
摘要
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Characterization of Target Gene Regulation by the Two Epstein-Barr Virus Oncogene LMP1 Domains Essential for B-cell Transformation.
B 细胞转化所必需的两个 Epstein-Barr 病毒癌基因 LMP1 结构域对靶基因调控的表征。
- DOI:10.1101/2023.04.10.536234
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Mitra,Bidisha;Beri,NinaRose;Guo,Rui;Burton,EricM;Murray-Nerger,LauraA;Gewurz,BenjaminE
- 通讯作者:Gewurz,BenjaminE
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Benjamin Elison Gewurz其他文献
Benjamin Elison Gewurz的其他文献
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{{ truncateString('Benjamin Elison Gewurz', 18)}}的其他基金
Characterization of Epstein-Barr Virus Subversion of the Host SMC5/6 Restriction Pathway
Epstein-Barr 病毒颠覆宿主 SMC5/6 限制途径的特征
- 批准号:
10679118 - 财政年份:2023
- 资助金额:
$ 50.74万 - 项目类别:
Methionine and PI3K Metabolism Drive CIMP in EBV Epithelial Cancers
蛋氨酸和 PI3K 代谢驱动 EBV 上皮癌中的 CIMP
- 批准号:
10627692 - 财政年份:2023
- 资助金额:
$ 50.74万 - 项目类别:
Regulation of the Epstein-Barr Virus Lytic Switch
Epstein-Barr 病毒裂解开关的调节
- 批准号:
10317642 - 财政年份:2021
- 资助金额:
$ 50.74万 - 项目类别:
Regulation of the Epstein-Barr Virus Lytic Switch
Epstein-Barr 病毒裂解开关的调节
- 批准号:
10445326 - 财政年份:2021
- 资助金额:
$ 50.74万 - 项目类别:
Epstein-Barr virus LMP1 mediated oncogenicity
EB 病毒 LMP1 介导的致癌性
- 批准号:
10676959 - 财政年份:2019
- 资助金额:
$ 50.74万 - 项目类别:
Epstein-Barr virus LMP1 mediated oncogenicity
EB 病毒 LMP1 介导的致癌性
- 批准号:
10020965 - 财政年份:2019
- 资助金额:
$ 50.74万 - 项目类别:
Metabolic Network Remodeling in Epstein-Barr Virus Lymphomagenesis
EB 病毒淋巴瘤发生中的代谢网络重塑
- 批准号:
9899193 - 财政年份:2018
- 资助金额:
$ 50.74万 - 项目类别:
Metabolic Network Remodeling in Epstein-Barr Virus Lymphomagenesis
EB 病毒淋巴瘤发生中的代谢网络重塑
- 批准号:
10353408 - 财政年份:2018
- 资助金额:
$ 50.74万 - 项目类别:
Genetic and Proteomic Analysis of Epstein-Barr Virus LMP1 Activation of NF-kB
EB 病毒 LMP1 激活 NF-kB 的遗传和蛋白质组学分析
- 批准号:
8284169 - 财政年份:2010
- 资助金额:
$ 50.74万 - 项目类别:
Genetic and Proteomic Analysis of Epstein-Barr Virus LMP1 Activation of NF-kB
EB 病毒 LMP1 激活 NF-kB 的遗传和蛋白质组学分析
- 批准号:
8068346 - 财政年份:2010
- 资助金额:
$ 50.74万 - 项目类别:
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