Preliminary studies have provided evidence for a possible retroviral etiology in Sjogren's Syndrome (SS; autoimmune exocrinopathy). The sera of a significant number of primary SS patients contained antibodies reactive with the major capsid protein of HIV, p24 (CA). In some cases reactivity to another gag protein p17 (MA) was also observed. A human intracisternal A-type particle (HIAP) was isolated from lymphoblastoid cells exposed to SS patient biopsy material. This retroviral particle is distinguishable from HIV by morphological and physical criteria, cellular distribution, and reverse transcriptase divalent cation preference. The overall goal of the proposed study is to genetically and immunochemically define the protein composition of this novel human retroviral particle, and its relationship to mechanisms of xerostomia in SS. The first specific aim this proposal is to detect and identify via polymerase chain reaction (PCR) the presence of HIAP cross-reactive with HIV p24. The second specific aim is to clone and express the probable (gag), protease (pro) and polymerase (pol) genes, and subclone the genes into plasmid systems permitting analysis of their products.
The third aim i s to model the cross-reactive, and additional, epitopes on these protein products, and otherwise, by expression in diverse systems, characterize the similarities and differences of these protein products, and otherwise, by expression in diverse systems, characterize the similarities and differences of these proteins with those of other known retroviruses.
The fourth aim i s to determine the reactivity of viral particles or cloned and expressed proteins, or derived peptides, with either antibodies or with appropriate """"""""sensitized"""""""" lymphocytes derived from patients or immunized animals, including use of monoclonal antibodies. We will also determine the reactivity of antibodies with human salivary or other exocrine tissues, and the relationship of such reactivities to those naturally occurring in SS. Finally, we will determine by PCR the frequency of HIAP in archival lip biopsies preserved over a 20 year period and in samples from current SS patients, and relevant autoantibodies in a series of SS patients, with relevant controls derived from non-SS cases, each in the same series. The proposed studies will provide basic information regarding a heretofore undescribed human retroviral particle that has a possible, although yet to be established, role in SS xerostomia and other types of autoimmunity.
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