Systemic polyomavirus genome increase and dissemination of capsid-defective genomes in mammary gland tumor-bearing mice

BALB/c mire that developed tumors 7 to 8 months following neonatal infectio n by polyomavirus (PYV) wild-type strain A2 were characterized with respect to the abundance and integrity of the viral genome in the tumors and in 12 nontumorous organs. These patterns were compared to those found in tumor-f ree mice infected in parallel. Six mice were analyzed in detail including F our sibling females with mammary gland tumors. In four of five mammary glan d turners, the viral genome had undergone a unique deletion and/or rearrang ement. Three tumor-resident genomes with an apparently intact large T codin g region were present in abundant levels in an unintegrated state. Two of t hese had undergone deletions and rearrangements involving the capsid genes and therefore Lacked the capacity to produce live virus. In the comparative organ survey, the tumors harboring replication-competent genomes contained by far the highest levels of genomes of any tissue. However, the levels of PYV genomes in other organs were elevated by up to 1 to 2 orders of magnit ude compared to those detected in the same organs of tumor-free mice. The g enomes found in the nontumorous organs had the same rearrangements as the g enomes residing in the tumors. The original wild-type genome was detected a t low levels in a few organs, particularly in the kidneys. The data indicat e that a systemic increase in the level of viral genomes occurred in conjun ction with the induction of tumors by PYV, The results suggest two novel hy potheses: (1) that genomes may spread from the tumors to the usual PW targe t tissues and (ii) that this dissemination may take place in the absence of capsids, providing an important path for a virus to escape from the immune response. This situation may offer a useful model for the spread of HPV ac companying HPV-induced oncogenesis.