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DNA Replication ofFirst-GenerationAdenovirus Vectors inTumor Cells Dirk S. SteinwaerderCheryl A. CarlsonAndré Lieber2000 год

DNA Replication of First-Generation Adenovirus Vectors in Tumor Cells
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: 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 between the efficiency of viral DNA replication and the status of p53, pRb, and p16. However, the amount of virus attached and internalized changed with the cell cycle, affecting the intracellular concentration of viral DNA and thereby the replication efficacy. Furthermore, infection with AdE1 - vectors caused a partial G2/M arrest or delay in cell cycle progression, which became more pronounced in consecutive cell cycles. Correspondingly, vector DNA replication was found to be enhanced in cells artificially arrested in G2/M. Our findings suggest that cell cycling and thus passing through G2/M supports AdE1- DNA replication in the absence of E1A/E1B. This has potential implications for the use of first-generation adenovirus vectors in tumor gene therapy.
Год издания: 2000
Авторы: Dirk S. Steinwaerder, Cheryl A. Carlson, André Lieber
Издательство: Mary Ann Liebert, Inc.
Источник: Human Gene Therapy
Ключевые слова: Virus-based gene therapy research, CAR-T cell therapy research, Cancer Research and Treatments
Другие ссылки: Human Gene Therapy (HTML)
PubMed (HTML)