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糖尿病的发病机制。
EB病毒特征的毛状白斑(HL)
基因在病变中的表达,考察个体的作用
EBV基因产物在调节上皮分化中的作用
研究EBV基因在本病皮损中的表达规律
与淋巴细胞比较。我们已经取得了重大进展
在实现这些目标方面取得了进展。的标志
HL是分化上皮中高水平的EBV复制。
因此,在未来的FIEV年,我们建议延长这些
包括上皮基因特征的研究
在HL中表达上调,并研究病毒与HL之间的相互作用
细胞基因。
到目前为止,人们对EB病毒的谱系知之甚少。
HL中的基因表达,几乎什么都不知道
皮损中上皮基因的表达。这样做的目的是
建议对HL中EBV基因的表达进行表征;
鉴定在h1中上调的细胞基因,并
描述在HL中表达的EBV基因产物的调控。
在接下来的五年里,使用我们创建的HlcDNA文库,我们
将继续扩大我们对EBV曲目的了解
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
也描述了HL中上调的细胞基因。这个
这些基因表达的地形和特异性将是
用原位杂交技术对HL组织和对照组织进行了研究。
细胞和病毒对EBV基因调控的研究
反式激活蛋白质,我们将通过以下方式诱导蛋白质表达
我们的HL基因文库。在文库中表达的蛋白质将是
用与启动子相对应的放射性标记DNA进行探针
选定的已知在HL中表达的EBV基因。克隆编码
这些蛋白质将从文库中分离出来,并具有特异性
候选细胞和/或病毒DNA结合蛋白的
用凝胶滞留试验进行研究。然后蛋白质就会
表达以研究其对荧光素酶启动子的影响
记者制度。
对HL的研究为确定EBV的特征提供了一个独特的机会
上皮性感染。上皮细胞感染起着重要作用
在EBV生命周期中的重要作用,并理解
EB病毒与细胞基因在发病机制中的相互作用
对理解其他疾病有更广泛的影响
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