Role of EBNA-1 in Eliciting Anti-dsDNA Antibodies

EBNA-1 在引发抗 dsDNA 抗体中的作用

基本信息

批准号：
7574568
负责人：
LINDA Ann SPATZ
金额：
$ 20.15万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7574568
关键词：
Address Affect Age-Years American Antibodies Antibody Formation Antigens Antinuclear Antibodies Arthritis Asians Autoimmune Diseases Autoimmune Process Binding Binding Sites Cells Chromosomes Chronic Clinical Complex DNA DNA Binding DNA-Binding Proteins Data Deletion Mutation Deposition Development Diagnosis Disease Epstein-Barr Virus Infections Epstein-Barr Virus Nuclear Antigens Etiology Exanthema Frequencies Glomerulonephritis Goals Hispanics Human Herpesvirus 4 Immunization Impaired cognition Inbred BALB C Mice Incidence Individual Kidney Lupus Lupus Erythematosus Mediating Mouse Strains Mus Mutation Native Americans Nuclear Antigens Nuclear Localization Signal Patients Peptides Play Polyomavirus Production Proteins Recombinants Reporting Ribonucleoproteins Role Sequence Homology Systemic Lupus Erythematosus Testing Time Vasculitis Viral Virus Virus Latency Woman base cross reactivity ds-DNA expression vector immunogenic prevent response vector viral DNA

项目摘要

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the production of antinuclear antibodies to ribonucleoproteins and double-stranded DNA (dsDNA). Approximately 1.5 million Americans are affected by this illness, the majority being women. The etiology of SLE is unknown, but several viruses in particular the Epstein-Barr virus (EBV) have been implicated. There is an increase in the frequency of EBV infection observed in SLE patients compared to normal individuals. Epstein-Barr Nuclear Antigen-1 (EBNA-1) is a major antigen involved in viral latency that contains binding sites for viral DNA as well as chromosomes. We previously demonstrated that mice expressing EBNA-1 develop antibodies to dsDNA. The major objective of this proposal is to define the mechanism by which EBNA-1 exposure leads to the production of anti-dsDNA antibodies and whether these anti-dsDNA antibodies are pathogenic and deposit in the kidney. We will also determine whether or not EBNA-1 must complex with eukaryotic DNA in order to elicit an anti-DNA response or whether anti-EBNA-1 antibodies cross-react with dsDNA. Finally, we will address if there are strain specific differences in responsiveness to EBNA-1 and the development of antidsDNA antibodies and if this is mediated by TH1 orTH2 cells.

全身性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其特征是产生核糖蛋白和双链DNA（DSDNA）的抗核抗体。约150万美国人受这种疾病的影响，大多数是女性。 SLE的病因尚不清楚，但是尤其是爱泼斯坦 - 巴尔病毒（EBV）的几种病毒已涉及。有所增加与正常个体相比，SLE患者观察到的EBV感染的频率。爱泼斯坦 - 巴尔核抗原1（EBNA-1）是参与病毒潜伏期的主要抗原，其中包含病毒DNA的结合位点作为以及染色体。我们以前证明表达EBNA-1的小鼠会产生抗体 dsdna。该提案的主要目的是定义EBNA-1暴露导致的机制抗DSDNA抗体的产生以及这些抗DSDNA抗体是否是致病性和存入肾脏。我们还将确定EBNA-1是否必须与真核DNA复合为了引起抗DNA反应，还是抗EBNA-1抗体与dsDNA交叉反应。最后，我们如果在对EBNA-1的反应性方面存在特定的菌株差异和抗AntidsDNA的发展是否存在特定差异抗体，如果这是由Th1 Orth2细胞介导的。