MOLECULAR PATHOGENESIS 0F HAIRY LEUKOPLAKIA
MOLECULAR PATHOGENESIS 0F HAIRY LEUKOPLAKIA
批准号:
6104724
负责人:
JOEL Michael PALEFSKY
金额:
$17.44万
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-05-01 至 2000-04-30
关键词:
Epstein Barr virus HIV infections biopsy cell growth regulation clinical research epithelium gene expression genetic library genetic promoter element genetic regulation genetic transcription host organism interaction human subject molecular cloning molecular pathology nucleic acid sequence opportunistic infections oral leukoplakia radiotracer subtraction hybridization tissue /cell culture virus genetics virus replication
中文摘要
本项目的重点是了解
通过表征爱泼斯坦巴尔病毒(EBV)的毛状白斑(HL)
基因表达在病变,检查个人的作用,
调节上皮分化的EBV基因产物,和
研究EB病毒基因在该病变中的表达调控,
与淋巴细胞相比。 我们取得了重大
为实现这些目标取得进展。 的标志
HL是EBV在分化上皮中的高水平复制。
因此,我们建议在未来五年,
包括上皮基因特征的研究
在HL中上调,并研究病毒和
细胞基因
迄今为止,对EBV的所有功能知之甚少,
HL中的基因表达,几乎没有什么是已知的
上皮细胞基因的表达。 其目的是
建议描述HL中EBV基因表达的特征;
表征Hl中上调的细胞基因,以及
表征HL中表达的EBV基因产物的调节。
在接下来的五年里,我们利用我们构建的HlcDNA文库,
将继续扩大我们对EB病毒的了解,
HL中表达的基因。 使用消减cDNA文库
从HL和临床正常的邻近组织中产生,我们将
还表征了HL中上调的细胞基因。 的
这些基因表达的拓扑学和特异性将被
在HL和对照组织中通过mRNA原位杂交研究。
研究细胞和病毒对EBV基因的调控
反式激活蛋白,我们将诱导蛋白质表达,
我们的HL cDNA文库 在文库中表达的蛋白质将被
用对应于启动子的放射性标记DNA进行探测
选择已知在HL中表达的EBV基因。 克隆编码
蛋白质将从文库中分离,并且特异性
候选的细胞和/或病毒DNA结合蛋白将
使用凝胶阻滞试验进行研究。 然后蛋白质会
研究它们对荧光素酶启动子的影响
报告人制度
HL的研究为表征EBV提供了独特的机会
上皮细胞感染。 上皮细胞的感染
在EBV的生命周期中的重要作用,并了解
EB病毒与细胞基因在发病机制中的相互作用
对人类语言的理解具有更广泛的意义,
EBV相关病变,包括鼻咽癌
和非霍奇金淋巴瘤
英文摘要
The focus of this project is to understand the pathogenesis of
hairy leukoplakia (HL) by characterizing Epstein Barr virus (EBV)
gene expression in the lesion, examining the role of individual
EBV gene products in modulating epithelial differentiation, and
studying regulation of EBV gene expression in this lesion for
comparison with that of lymphocytes. We have made significant
progress toward achieving each of these aims. The hallmark of
HL is high level EBV replication in differentiated epithelium.
In the next fiev years,we therefore propose to extend these
studies to include characterization of epithelial genes
upregulated in HL, and to study the interaction between viral and
cellular genes.
To date, relatively little is known about the repertoire of EBV
gene expression within HL, and almost nothing is known of
epithelial gene expression in the lesion. The aims of this
proposal are to characterize EBV gene expression in HL; to
characterize cellular genes upregulated in Hl, and to
characterize the regulation of EBV gene products expressed in HL.
In the next five years, using an HlcDNA library we generated, we
will continue to expand our knowledge of the repertoire of EBV
genes expressed in HL. Using a subtraction cDNA library
generated from HL and clinically normal adjacent tissues, we will
also characterize cellular genes upregulated in HL. The
topography and specificity of expression of these genes will be
studied in HL and control tissues by mRNA in situ hybridization.
To study the regulation of EBV genes by cellular and viral
transactivating proteins, we will induce protein expression by
our HL cDNA library. Proteins expressed in the library will be
probed with radiolabeled DNA corresponding to promoters of
selected EBV genes known to be expressed in HL. Clones encoding
the proteins will be isolated from the library, and specificity
of the candidate cellular and/or viral DNA binding proteins will
be studied using gel retardation assays. The proteins will then
be expressed to study their effect on the promoter in luciferase
reporter system.
Studies of HL offer a unique opportunity to characterize EBV
infection of epithelium. Infection of epithelium plays an
important role in the EBV live cycle, and understanding the
interaction between EBV and cellular genes in the pathogenesis
of HL has broader implications for understanding of other
EBV-associated lesions as well, including nsaopharyngeal cancer
and non-Hodgkin's lymphoma.
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海外基金