Kinetics of HPV11 DNA replication after infection of keratinocytes with virions

Human papillomavirus type 11 (HPV11) normally infects keratinocytes of stratified epithelia and replicates as an episome. To untangle early events in the development of a papilloma, we have infected human keratinocytes with human papillomavirus type 11 virions and monitored replication using density labeling with bromodeoxyuridine and subsequent density centrifugation. We show that only a portion of the virus reaching the nucleus undergoes replication and that continued replication occurs without recruitment from the nonreplicating pool of virus suggesting that HPV11 replication remains confined to a small number of cells. Increasing inoculum size leads to more viral DNA reaching the nucleus but not a corresponding increase in viral replication. Subsequent papilloma development must, therefore, occur within a small subset of cells.