We have previously demonstrated that experimental expression of the polyomavirus transcription factor T-antigen has the potential to induce anti-DNA antibodies in mice. Two sets of independent evidences are presented here that demonstrate a biological relevance for this model.

A role for polyomaviruses in the pathogenesis of systemic lupus erythematosus (SLE) has been suggested. BK virus (BKV) and JC virus (JCV) were demonstrated in single urine specimens from 7 (16%) of 44 and 5 (11%) of 44 patients with SLE and 0/88 and 18 (21%) of 88 matched healthy controls, respectively. During a 1-year follow-up study, episodes of polyomaviruria were detected in 16 (80%) of 20 patients, BKV in 13, and JCV in 3 patients. A group of 12 (60%) of 20 patients demonstrated persistent or recurrent polyomaviruria, BKV viruria (n=9), or JCV viruria (n=3) in 180 (70%) of 256 specimens. Polyomaviruria was not significantly associated with immunosuppressive therapy. The BKV and JCV isolates revealed predominantly stable archetypal regulatory regions over 3 years, indicating viral persistence rather than reinfection as a cause for urinary shedding. The demonstration of nondetectable viremia and stable archetypal BKV and JCV noncoding control regions during persistent viruria argue against the urinary tract as a focus for the creation of rearranged regulatory region variants.

We have recently demonstrated that polyomavirus BK and isolated BK double-stranded (ds)DNA have a strong potential for induction of anti-dsDNA antibodies. Here, data are presented that demonstrate that normal mice (a term used in this report for mice not predisposed to a lupus-like syndrome) of four different strains responded to both BK virus and BK dsDNA by producing transient antibodies binding preferentially to the viral dsDNA itself. These antibodies did not bind in the Crithidia luciliae assay, and did not seem to be of pathogenic significance, as neither signs of proteinuria nor immunochemical signs of glomerulonephritis developed in these mice. In contrast, 5-week-old (NZBxNZW)F1 mice developed strong and persistent anti-dsDNA antibodies in response to BK virus and BK dsDNA, with similar features to those of anti-dsDNA antibodies from individuals with systemic lupus erythematosus: they reacted strongly in the Crithidia luciliae assay and cross-reacted with viral as well as with mammalian dsDNA. Furthermore, persistent proteinuria and glomerulonephritis, with demonstrable heavy mesangial deposits of immune complexes containing IgG anti-dsDNA antibodies, developed 2-3 months earlier than in spontaneously autoimmune control mice. The relevance of these observations to a viral origin of anti-dsDNA antibodies in lupus is discussed.