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 kerat inocytes with human papillomavirus type 11 virions and monitored repli cation using density labeling with bromodeoxyuridine and subsequent de nsity centrifugation. We show that only a portion of the virus reachin g the nucleus undergoes replication and that continued replication occ urs without recruitment from the nonreplicating pool of virus suggesti ng 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 pap illoma development must, therefore, occur within a small subset of cel ls.