Suppression mechanism of Geminivirus-encoded TrAP protein
双子病毒编码的TrAP蛋白的抑制机制
基本信息
- 批准号:10389066
- 负责人:
- 金额:$ 4.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-12-21 至 2022-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnimal ModelArabidopsisBindingBiochemicalChromatinDNADNA Virus InfectionsDNA VirusesDefense MechanismsDiseaseEpigenetic ProcessEukaryotaExhibitsFactor VFamilyFunctional disorderGeminiviridaeGene SilencingGene Silencing PathwayGenesGeneticGenetic TranscriptionGoalsHistonesHost DefenseHumanImmune responseInfectionInnate Immune ResponseInnate Immune SystemKnowledgeLaboratoriesMethylationModelingMolecularNuclearPathogenicityPathway interactionsPhysiologicalPlantsPredispositionPreventive measureProteinsProteomicsRNA InterferenceRaceResearchRoleSingle Stranded DNA VirusViralVirusVirus DiseasesVirus LatencyWorkarmdefense responseepigenetic silencinghistone demethylasehistone methyltransferaseinsightloss of functionmutantparalogous genepathogenscreeningvirus host interaction
项目摘要
The primary goal of the proposed research is to elucidate the mechanism of host innate immune
responses and viral counter-defense responses at an epigenetic level. Eukaryotes have evolved sophisticated
mechanisms of RNA silencing to defense invasive viruses. On the other hand, viruses including those infecting
humans encode proteins, referred to as viral suppressors, to block silencing pathways to evade host
surveillance. The prevailing worldwide study on host-virus interaction focuses on the antivirus role of
posttranscriptional gene silencing (PTGS) and viral suppression of PTGS. While our knowledge of viral
suppression at the PTGS level has been drastically expanded, our understanding of viral suppression at the
level of transcriptional gene silencing (TGS) is very poor. In eukaryotes, the nuclear DNA is wrapped onto
histone octamers to form a chromatin. Chromatin methylation not only regulates gene replication and
transcription, but also controls the latency of viruses in human and plants, functioning as an innate immune
system to restrict invasive pathogens. Recent research from the PI's group and other laboratories has
illuminated that TrAP suppressor encoded by Geminivirus, a family of single-stranded DNA viruses in the
model organism Arabidopsis, genetically interferes with the TGS pathway. By proteomic screening of cellular
factors, the PI's group has identified that a histone methyltransferase (SUVH4) and a histone demethylase
(REF6), two key effectors in the TGS pathway, are new bona fide targets by TrAP. These results and work
from several other groups led to conceptualization of a model that TGS serves as a defense mechanism to
defend invasive DNA pathogens, whereas viral suppressors can break this restriction by directly inhibiting the
TGS integrators. To address this model, the PI proposes: 1) to determine the biochemical basis for specific
inhibitory effect of TrAP on SUVH. The PI wishes to pinpoint the critical residues of TrAP that participate in the
interaction with SUVH4 and investigate how the residues affect SUVH4 function and alter the viral
pathogenicity; The PI will also study whether TrAP targets the genetic paralogs of SUVH4 such as SUVH5 and
SUVH6 to regulate Geminivirus infection; and 2) to investigate function and mechanism of TrAP-REF6
interaction in viral infection. The PI laboratory has observed that REF6 binds to Geminivirus chromatin and
loss-of-function mutants of ref6 exhibit reduced susceptibility to Geminivirus infection. The PI plans to
systemically study the biochemical features of REF6 and its functional interaction of TrAP in viral transcription
and multiplication. The proposed study will address the fundamental but poorly understood mechanism how
histone methyltransferases and demethylases coordinately confer viral latency and how DNA virus co-opts to
hijack the critical TGS components as counter-defense responses. The suppression mechanism of TrAP may
be exploited for directed therapies or preventative measures to address physiological disorders that arise from
epigenetic dysfunction in eukaryotes including human.
本研究的主要目的是阐明宿主先天免疫的机制
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
In vitro Reconstitution Assays of Arabidopsis 20S Proteasome.
拟南芥 20S 蛋白酶体的体外重建测定。
- DOI:10.21769/bioprotoc.3967
- 发表时间:2021
- 期刊:
- 影响因子:0.8
- 作者:Li,Yanjun;Sun,Di;Yan,Xingxing;Wang,Zhiye;Zhang,Xiuren
- 通讯作者:Zhang,Xiuren
Intrinsically disordered proteins SAID1/2 condensate on SERRATE for dual inhibition of miRNA biogenesis in Arabidopsis.
- DOI:10.1073/pnas.2216006120
- 发表时间:2023-04-04
- 期刊:
- 影响因子:11.1
- 作者:Shang, Baoshuan;Wang, Lin;Yan, Xingxing;Li, Yanjun;Li, Changhao;Wu, Chaohua;Wang, Tian;Guo, Xiang;Choi, Suk Won;Zhang, Tianru;Wang, Ziying;Tong, Chun-Yip;Oh, Taerin;Zhang, Xiao;Wang, Zhiye;Peng, Xu;Zhang, Xiuren
- 通讯作者:Zhang, Xiuren
H3.1K27me1 loss confers Arabidopsis resistance to Geminivirus by sequestering DNA repair proteins onto host genome.
- DOI:10.1038/s41467-023-43311-1
- 发表时间:2023-11-18
- 期刊:
- 影响因子:16.6
- 作者:Wang, Zhen;Castillo-Gonzalez, Claudia M.;Zhao, Changjiang;Tong, Chun-Yip;Li, Changhao;Zhong, Songxiao;Liu, Zhiyang;Xie, Kaili;Zhu, Jiaying;Wu, Zhongshou;Peng, Xu;Jacob, Yannick;Michaels, Scott D.;Jacobsen, Steven E.;Zhang, Xiuren
- 通讯作者:Zhang, Xiuren
scInTime: A Computational Method Leveraging Single-Cell Trajectory and Gene Regulatory Networks to Identify Master Regulators of Cellular Differentiation.
- DOI:10.3390/genes13020371
- 发表时间:2022-02-18
- 期刊:
- 影响因子:3.5
- 作者:Xu Q;Li G;Osorio D;Zhong Y;Yang Y;Lin YT;Zhang X;Cai JJ
- 通讯作者:Cai JJ
The epigenetic factor FVE orchestrates cytoplasmic SGS3-DRB4-DCL4 activities to promote transgene silencing in Arabidopsis.
- DOI:10.1126/sciadv.abf3898
- 发表时间:2021-08
- 期刊:
- 影响因子:13.6
- 作者:Sun D;Li Y;Ma Z;Yan X;Li N;Shang B;Hu X;Cui K;Koiwa H;Zhang X
- 通讯作者:Zhang X
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Xiuren Zhang其他文献
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{{ truncateString('Xiuren Zhang', 18)}}的其他基金
Roles of SWI/SNF complexes in posttranscriptional processing of RNA
SWI/SNF 复合物在 RNA 转录后加工中的作用
- 批准号:
10355465 - 财政年份:2019
- 资助金额:
$ 4.31万 - 项目类别:
Roles of SWI/SNF complexes in posttranscriptional processing of RNA
SWI/SNF 复合物在 RNA 转录后加工中的作用
- 批准号:
10191950 - 财政年份:2019
- 资助金额:
$ 4.31万 - 项目类别:
Roles of SWI/SNF complexes in posttranscriptional processing of RNA
SWI/SNF 复合物在 RNA 转录后加工中的作用
- 批准号:
9905546 - 财政年份:2019
- 资助金额:
$ 4.31万 - 项目类别:
Suppression mechanism of Geminivirus-encoded TrAP protein
双生病毒编码的TrAP蛋白的抑制机制
- 批准号:
10294234 - 财政年份:2018
- 资助金额:
$ 4.31万 - 项目类别:
Suppression mechanism of Geminivirus-encoded TrAP protein
双子病毒编码的TrAP蛋白的抑制机制
- 批准号:
10059255 - 财政年份:2018
- 资助金额:
$ 4.31万 - 项目类别:
Pathogenesis Mechanism of Geminivirus-Encoded AL2
双生病毒编码的AL2的发病机制
- 批准号:
8223862 - 财政年份:2012
- 资助金额:
$ 4.31万 - 项目类别:
Pathogenesis Mechanism of Geminivirus-Encoded AL2
双生病毒编码的AL2的发病机制
- 批准号:
8416325 - 财政年份:2012
- 资助金额:
$ 4.31万 - 项目类别:
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