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