Antibodies to Eukaryotic, including Autologous, Native DNA are Produced during BK Virus Infection, but not after Immunization with Non‐Infectious BK DNA

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Abstract
The contemporary view concerning the origin of anti-dsDNA antibodies is that eukaryotic dsDNA is not immunogenic. Results presented here, however, show (1) that inoculation of rabbits with BK virus elicits antibodies to eukaryotic, including autologous, dsDNA, (2) that the transition from a non-immunogenic to an immunogenic state of autologous dsDNA depends on productive infection with BK virus, and (3) that inoculation with protein-free circular BK dsDNA initiates both infection in vivo and production of antibodies to autologous dsDNA. Non-infectious linearized BK dsDNA did not elicit any anti-dsDNA antibodies, while the same DNA molecule, when complexed with methylated bovine serum albumin, elicited anti-dsDNA antibodies solely recognizing BK dsDNA. Neither of the two linearized BK dsDNA preparations initiated infection. Using two different techniques, we could demonstrate that two separate sets of anti-dsDNA antibodies were produced during viral infection; one recognizing BK dsDNA, and the other recognizing autologous dsDNA. Thus, in contrast to previous assumptions, autologous dsDNA may be immunogenic. Based on the present results, we propose that autologous dsDNA can be rendered immunogenic through complex formation with viral DNA binding protein(s) such as the structural protein VP1 or the tumour antigen T. Such DNA-protein complexes may bypass a putative T-cell tolerance to autologous dsDNA.