The role of the Epstein Barr Virus Nuclear Antigen-1 in the production of antibodies to dsDNA
Item
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Title
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The role of the Epstein Barr Virus Nuclear Antigen-1 in the production of antibodies to dsDNA
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Identifier
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d_2009_2013:f8ea76ebca15:11224
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identifier
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11582
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Creator
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Yadav, Pragya,
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Contributor
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Linda Spatz
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Date
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2012
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biochemistry | Immunology | Virology
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Abstract
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Previous studies have shown an association between the Epstein Barr Virus (EBV) and the development of the autoimmune disease, Systemic Lupus Erythematosus (SLE). However, it has not yet been proven that EBV plays a causative role in the etiology of SLE. In the present study, I demonstrate that mice injected with the major EBV nuclear protein, EBNA-1, can develop antibodies to double stranded DNA (dsDNA), which are the hallmark of SLE. To understand the basis for the anti-dsDNA response, I generated monoclonal antibodies (MAbs) to EBNA-1 from EBNA-1 injected mice. I made the novel observation that some of these MAbs cross-react with dsDNA. One of these MAbs, designated 3D4, was shown to bind to the glomeruli of mouse kidneys. This is a feature of the pathogenic anti-dsDNA antibodies in lupus, which can deposit in the kidney and cause renal damage (nephritis).;In an effort to map the epitope in EBNA-1 that elicits cross-reactivity to dsDNA, I generated several truncated fragments of the EBNA-1 protein and examined the binding of the cross-reactive MAbs to these fragments. All of the cross-reactive MAbs that I examined recognized an epitope that resides within amino acids 459 and 607 in the carboxyl region of EBNA-1. This 148 amino acid region is confined to the viral binding site (VBS) of EBNA-1 and contains a well-defined secondary structure, although, it is not yet known whether the epitope is linear or conformational. We are currently trying to map this epitope further to define a smaller peptide that these MAbs recognize. Identification of a small epitope that serves as a peptide mimic for dsDNA may help in the design of diagnostic strategies for screening and therapeutic strategies for treating patients with SLE.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biochemistry
