Inoculation with BK virus may break immunological tolerance to histone and DNA antigens

BK virus particles contain histones of host cell origin that combine with viral DNA to form minichromosomes. Data from earlier immunoblotting experiments demonstrated that rabbits inoculated i.v. with purified infectious BK virus produced antibodies not only to the viral structural protein VP1 but also to migrating polypeptides of a molecular mass ranging from 14-16 kDa. These proteins were believed to represent certain histone classes. To examine this hypothesis, sera from five rabbits inoculated with BK virus were analyzed by ELISA for antibodies against polynucleosomes, the individual histone classes, and double-stranded DNA, as well as against antigens carried by the structural viral proteins. Antibodies against polynucleosomes and also against histones H1 and H3 were found in sera from two of five inoculated rabbits. The same sera contained antibodies reacting with double-stranded DNA, whereas no antibodies against H2A, H2B, and H4 were detected. BK virus inoculation may thus lead to a break of tolerance, resulting in autoantibody production against highly conserved antigens that, in this context, may be regarded as "self-antigens", irrespective of the species in which they originate.