ROLE OF CHROMATIN IN HERPES SIMPLEX VIRUS TYPE 1 (HSV-1) GENE REGULATION
染色质在 1 型单纯疱疹病毒 (HSV-1) 基因调控中的作用
基本信息
- 批准号:7959469
- 负责人:
- 金额:$ 10.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-05-01 至 2010-04-30
- 项目状态:已结题
- 来源:
- 关键词:AlkaloidsAnimal ModelAntiviral AgentsBiomedical ResearchCell LineCellsChromatinCollaborationsComplexComputer Retrieval of Information on Scientific Projects DatabaseCorneaDataElementsExhibitsEye InfectionsFundingGene ExpressionGene Expression RegulationGene SilencingGenetic TranscriptionGrantHerpesvirus 1Histone H4HormonesIn VitroInfectionInstitutionLaboratory StudyLigandsLouisianaLyticMolecular and Cellular BiologyNeuronsRecruitment ActivityResearchResearch PersonnelResourcesRoleSMARCA4 geneSourceThyroid Hormone ReceptorTimeTransfectionUnited States National Institutes of HealthVirusVirus DiseasesVirus Latencyin vivolatent infectionmanzamine Apreventpromoter
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Our laboratory studies the molecular and cellular biology of HSV-1 during lytic and latent infections including the mechanisms of gene silencing and reactivation. We investigated the roles of TR and T3 on HSV-1 gene expression in vitro after identifying the thyroid hormone receptor (TR) responsive elements (TREs) in the promoters of HSV-1 TK and LAT. We demonstrated that liganded TR repressed TK promoter activity by transfection and infection of neuronal cells. Our data also showed that the liganded TRs activated LAT transcription but repressed ICP0 transcription. TRs were recruited to these promoters independently of T3 and hyperacetylated histones H4 was associated with these promoters in the presence of hormone. In addition, various chromatin modifying complexes such as CTCF and BRG1 complexes were recruited to these promoters in the presence of TR and T3. Furthermore, T3-treated N2aTR¿ cells were suppressive to TK expression and virus egress at low moi but the abstraction of hormone enhanced the TK expression and thus increased the release of infectious viruses. These results, for the first time, suggested that T3 could regulate the HSV-1 infections and may have a role in viral latency and reactivation in vivo. Studies using animal models are underway.
We also investigate a candidate antiviral drugs that we have developed in collaboration with Dr. El Sayed. The results showed that an alkaloid Manzamine A exhibits significant inhibitory effect on viral infection in a corneal cell line at 1¿M. These results suggest that it may have great potential to prevent HSV-1 induced eye infection.
这个子项目是许多研究子项目中利用
资源由NIH/NCRR资助的中心拨款提供。子项目和
调查员(PI)可能从NIH的另一个来源获得了主要资金,
并因此可以在其他清晰的条目中表示。列出的机构是
该中心不一定是调查人员的机构。
我们的实验室研究了HSV-1在裂解和潜伏感染期间的分子和细胞生物学,包括基因沉默和重新激活的机制。在鉴定了HSV-1的TK和LAT启动子中的甲状腺激素受体反应元件(TRES)后,我们研究了TRR和T3在体外对HSV-1基因表达的影响。我们通过神经细胞的转染和感染证明了连接的tr抑制了TK启动子的活性。我们的数据还表明,连接的TRs激活了LAT转录,但抑制了ICP0转录。在激素存在的情况下,这些启动子独立于T3和高乙酰化组蛋白H4被招募到这些启动子上。此外,在tr和t3存在的情况下,不同的染色质修饰复合体,如CTCF和BRG1复合体被招募到这些启动子上。此外,在低MOI时,T3处理的N2aTR细胞对TK的表达和病毒的排出有抑制作用,但激素的提取促进了TK的表达,从而增加了感染性病毒的释放。这些结果首次表明,T3可以调节HSV-1的感染,并可能在体内对病毒的潜伏和重新激活起作用。使用动物模型的研究正在进行中。
我们还研究了我们与El Sayed博士合作开发的一种候选抗病毒药物。结果表明,生物碱甘露糖胺A在1M的角膜细胞株中对病毒感染有明显的抑制作用,提示其在预防HSV-1诱导的眼部感染方面有很大的潜力。
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)
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Shaochung Victor Hsia其他文献
The expanding functions of thyroid hormone
- DOI:
10.1186/s13578-017-0176-0 - 发表时间:
2017-10-19 - 期刊:
- 影响因子:6.200
- 作者:
Jiemin Wong;Shaochung Victor Hsia - 通讯作者:
Shaochung Victor Hsia
Shaochung Victor Hsia的其他文献
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{{ truncateString('Shaochung Victor Hsia', 18)}}的其他基金
Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
核激素受体对 HSV-1 基因表达和复制的调节
- 批准号:
8731283 - 财政年份:2012
- 资助金额:
$ 10.79万 - 项目类别:
Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
核激素受体对 HSV-1 基因表达和复制的调节
- 批准号:
8551783 - 财政年份:2012
- 资助金额:
$ 10.79万 - 项目类别:
Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
核激素受体对 HSV-1 基因表达和复制的调节
- 批准号:
8915764 - 财政年份:2012
- 资助金额:
$ 10.79万 - 项目类别:
Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
核激素受体对 HSV-1 基因表达和复制的调节
- 批准号:
8421556 - 财政年份:2012
- 资助金额:
$ 10.79万 - 项目类别:
REGULATION OF HSV-1 GENE EXPRESSION AND REPLICATION BY NUCLEAR HORMONE RECEPTORS-Research Supplement
核激素受体对 HSV-1 基因表达和复制的调节 - 研究补充
- 批准号:
8848528 - 财政年份:2012
- 资助金额:
$ 10.79万 - 项目类别:
Mechanisms of Early Growth Response Factor 1 (Egr-1) Induction by HSV-1 Lytic Inf
HSV-1 Lytic Inf 诱导早期生长反应因子 1 (Egr-1) 的机制
- 批准号:
7939557 - 财政年份:2010
- 资助金额:
$ 10.79万 - 项目类别:
Mechanisms of Early Growth Response Factor 1 (Egr-1) Induction by HSV-1 Lytic Inf
HSV-1 Lytic Inf 诱导早期生长反应因子 1 (Egr-1) 的机制
- 批准号:
8112129 - 财政年份:2010
- 资助金额:
$ 10.79万 - 项目类别:
ROLE OF CHROMATIN IN HERPES SIMPLEX VIRUS TYPE 1 (HSV-1) GENE REGULATION
染色质在 1 型单纯疱疹病毒 (HSV-1) 基因调控中的作用
- 批准号:
7720007 - 财政年份:2008
- 资助金额:
$ 10.79万 - 项目类别:
ROLE OF CHROMATIN IN HERPES SIMPLEX VIRUS TYPE 1 (HSV-1) GENE REGULATION
染色质在 1 型单纯疱疹病毒 (HSV-1) 基因调控中的作用
- 批准号:
7609953 - 财政年份:2007
- 资助金额:
$ 10.79万 - 项目类别:
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