ROLE OF MURINE LEUKEMIA VIRUS IN AUTOIMMUNITY

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DESCRIPTION (adapted from applicant's abstract): Retroviruses have been associated with human and murine autoimmune disease, although definitive proof that these retroviruses cause the autoimmune state is lacking. Murine leukemia viruses (MuLV) are retroviruses that may be endogenously expressed. Immune complexes containing MuLV products are found in autoimmune mice. Abnormal expression of MuLV transcripts has also been found. Studies proposed in this application will test the hypothesis that MuLV or the immune response to MuLV plays a role in the development of autoimmunity in mice carrying the lpr mutation. The applicant has demonstrated the existence of at least two potentially novel infectious retroviruses which appear to be produced by B cells of C3H lpr mice but cannot be detected in wild type or MRL lpr mice. Viremia begins to be detectable at about three months of age, suggesting that either the virus may be a recombinant (as in the AKR system), or could be an endogenous retrovirus which is normally transcriptionally silent, but whose expression is induced secondarily as a result of the development of autoimmune disease and polyclonal immune activation. The first aim of the proposal is to determine the nucleic acid sequence of the novel retroviruses. Preliminary data indicates successful cloning and sequencing of an expressed retrovirus. The second aim is to study the expression of this retrovirus in different tissues from mice of different genetic backgrounds. The third aim is to correlate the expression of the antibody response to the retrovirus with the production of autoantibodies and to determine whether the anti-retrovirus antibodies are present in immune complexes from diseased kidneys.