DNA Replication of First-Generation Adenovirus Vectors in Tumor Cells

A major role of the early gene 1A and 1B products (E1A and E1B) in adenovirus infection is to create a cellular environment appropriate for viral DNA replication. This is, in part, achieved by inactivation of tumor suppressor gene products such as pRb or p53. The functions of these same cellular proteins are also frequently lost in tumor cells. Therefore, we hypothesized that tumor cell lines with deregulated p53 and/or pRb pathways might support replication of E1A/E1B-deleted, first-generation adenovirus vectors (AdE1-). Here, we analyzed the impact of virus uptake, cell cycling, and the status of cell cycle regulators on AdE1- DNA synthesis. Cellular internalization of AdE1- vectors varied significantly among different tumor cell lines, whereas nuclear import of incoming viral DNA appeared to be less variable. Replication assays performed under equalized infection conditions demonstrated that all analyzed tumor cell lines supported AdE1- synthesis to varying degrees. There was no obvious correlation bet...