Mutagenic activity of BKV and JCV in human and other mammalian cells

Abstract

We present data suggesting that human polyomaviruses BKV and JCV, widely distributed throughout human populations, are able to induce gene mutations in cultured cells. In this study, using different infecting agents, cell lines to be infected, mutation expression periods, and selection systems, we observed mutagenic effects of varying extent with values of spontaneous mutant frequencies being increased after BKV infection up to 100-fold in BHK cells (6-thioguanine resistance) and nearly 35-fold in virus-transformed human Lesch-Nyhan cells (ouabain resistance). In experiments with BKV the viral mutagenic potential was found to be raised both in moderately uv-irradiated cells, or when wild-type virus was replaced by the variant BKV-IR isolated from a human tumor. Since BKV-IR is defective in the expression of small-t antigen, the viral mutagenicity does not require this protein to be active. BKV was shown to mutate, besides different established cell lines, human peripheral blood lymphocytes. Moreover, as demonstrated by comparing mutagenicities of DNAs from BKV, JCV, and the related polyomavirus SV40, the mutagenic effects of the three viruses do not appear to be essentially different. Implications of these findings are discussed.