ORGAN-SPECIFIC AND AGE-SPECIFIC REPLICATION OF POLYOMAVIRUS IN MICE

A novel organ- and age-specific pattern of polyomavirus DNA replication in mice is described. Two broadly defined classes of response to polyomavirus infection were observed: class I organs (mammary gland, bone, and skin) responded with high levels of replication in neonate mice and moderate levels in adults; class II organs (kidney, liver, and lung) responded with high levels in neonates and very low levels in adults. Thus, aging affected replication in all organs, and organ specificity was superimposed on this age-related decrease. We argue that the organ- and age-specific pattern likely reflects in part the activities of a multiplicity of general or tissue-specific, age-dependent transcription factors, which modulate viral replication or viral transcription or both. Interestingly, the majority of tumors in mice infected as neonates or as immunoincompetent adults originate in class I organs, suggesting that the ability to replicate in adult tissues is an important factor controlling polyomavirus oncogenesis. From the analysis of the infection process in adult mammary glands, a novel mode of polyomavirus infection emerged which contrasts with that derived from observations of tissue culture systems. A nonproductive infection was seen, characterized by very low levels of live virus (in the range of 10(-4) PFU per cell) and maintenance of the viral genome in an unintegrated, moderately replicating state. Maintenance of the viral genome was accomplished without integration into host cell DNA in all three tumor-prone organs, both prior to as well as beyond oncogenesis.