EXPERIMENTAL EXPRESSION IN MICE AND SPONTANEOUS EXPRESSION IN HUMAN SLE OF POLYOMAVIRUS T-ANTIGEN - A MOLECULAR-BASIS FOR INDUCTION OF ANTIBODIES TO DNA AND EUKARYOTIC TRANSCRIPTION FACTORS

We have previously demonstrated that experimental expression of the po lyomavirus transcription factor T-antigen has the potential to induce anti-DNA antibodies in mice. Two sets of independent evidences are pre sented here that demonstrate a biological relevance for this model. Fi rst, we describe results demonstrating that mice inoculated with T-ant igen-expressing plasmids produced antibodies, not only to T-antigen an d DNA, but also to the DNA-binding eukaryotic transcription factors TA TA-binding protein (TBP), and to the cAMP-response-element-binding pro tein (CREB). Secondly, we investigated whether polyomavirus reactivati on occurs in SLE patients, and whether antibodies to T-antigen, DNA, a nd to TBP and CREB are linked to such events. Both within and among th ese SLE patients, frequent polyomavirus reactivations were observed th at could not be explained by certain rearrangements of the noncoding c ontrol regions, nor by corticosteroid treatment. Linked to these event s, antibodies to T-antigen, DNA, TBP, and CREB were detected, identica l to what we observed in mice. Antibodies recognizing double-stranded DNA were confined to patients with frequent polyomavirus reactivations . The results described here indicate that cognate interaction of B ce lls recognizing DNA or DNA-associated proteins and T cells recognizing T antigen had taken place as a consequence of complex formation betwe en T ag and DNA in vivo in the context of polyomavirus reactivations.