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The Role of Hepatitis Delta Virus in Sjogren's Syndrome

丁型肝炎病毒在干燥综合征中的作用

基本信息

批准号：
9750710
负责人：
Melodie Lynn Weller
金额：
$ 24.8万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-07-31
项目状态：
已结题

项目摘要

Sjögren's syndrome (SS) is an autoimmune disease of unknown etiology. It is the second most common autoimmune disease with predominance noted in females compared to makes (9:1). Strong evidence exists supporting a viral etiology of SS, but as of yet a direct cause and effect relationship has not been established. It is our hypothesis that more than one virus may be able to trigger the development of SS. To get a better picture of the viruses present in salivary glands of SS patients, we used a custom viral microarray chip to identify virus profiles in the salivary glands of SS patients and healthy volunteers. Using this platform, we have identified a distinct cohort of SS patients positive for Hepatitis Delta Virus (HDV). Our preliminary data has revealed not only the presence of HDV sequence in salivary glands of a subset of SS patients, but also the presence of HDV antigen. Making this viral profile more unique, these patients have tested negative for Hepatitis B virus antigen and antibody, the only known helper virus of HDV. This proposal aims to define the role of HDV in SS and determine if a direct cause-and-effect relationship exists between expression of the HDV antigen or genome and altered salivary gland function. In vitro studies will evaluate the impact of HDV antigen or genome expression and cellular function in salivary gland cell lines. Next, in vivo studies will evaluate expression of HDV antigen and genome in mouse salivary glands. Evaluation of an autonomous HDV infection in an intact system will define the ability of HDV to initiate a SS-like phenotype. The third aim of this grant will deliver a test to detect low-level HDV infection specifically in salivary gland tissue and identify correlations between levels of HDV in salivary gland and those identified in serum or saliva. Identification of HDV sequence and antigen in the salivary glands of pSS patients is a significant discovery in the field of Sjögren's syndrome research and stands to greatly impact the current therapeutic approaches used to treat this autoimmune disease.

干燥综合征（SS）是一种病因不明的自身免疫性疾病。它是第二种最常见的自身免疫性疾病，女性比较（9：1）。有强有力的证据表明 SS的病因学，但迄今为止尚未有直接的因果关系，确立了习我们的假设是不止一种病毒 SS的发展。为了更好地了解唾液中存在的病毒 SS患者的腺体，我们使用定制的病毒微阵列芯片来鉴定病毒 SS患者和健康志愿者唾液腺中的分布。使用此平台，我们已经确定了一个独特的队列SS患者肝炎阳性 Delta病毒（HDV）。我们的初步数据显示，在SS患者的一个子集的唾液腺中的HDV序列，而且 HDV抗原的存在。使这种病毒特征更加独特，这些患者 B型肝炎病毒抗原和抗体检测呈阴性， HDV辅助病毒。该提案旨在确定HDV在SS中的作用，确定表达之间是否存在直接因果关系 HDV抗原或基因组和唾液腺功能改变。体外研究将评估HDV抗原或基因组表达和细胞的影响，在唾液腺细胞系中的功能。接下来，体内研究将评估表达 HDV抗原和基因组在小鼠唾液腺中的表达。评价一个完整系统中的自主HDV感染将定义HDV的能力，启动SS样表型。这笔赠款的第三个目标将提供一个测试，低水平HDV感染，特别是在唾液腺组织中并识别唾液腺中HDV水平与血清或唾液。唾液中丁型肝炎病毒基因序列及抗原的鉴定 pSS患者的腺体是干燥病领域的重大发现，综合征研究，并将极大地影响目前的治疗用于治疗这种自身免疫性疾病的方法。