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Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity.

Authors
  • Clodagh O'Shea
  • L, Johnson
  • B, Bagus
  • S, Choi
  • C, Nicholas
  • A, Shen
  • L, Boyle
  • K, Pandey
  • C, Soria
  • J, Kunich
  • Y, Shen
  • G, Habets
  • D, Ginzinger
  • F, Mccormick
Type
Published Article
Journal
Cancer Cell International
Publisher
Springer (Biomed Central Ltd.)
Volume
6
Issue
6
Pages
611–623
Source
O'Shea Lab
License
Unknown

Abstract

ONYX-015 is an adenovirus that lacks the E1B-55K gene product for p53 degradation. Thus, ONYX-015 was conceived as an oncolytic virus that would selectively replicate in p53-defective tumor cells. Here we show that loss of E1B-55K leads to the induction, but not the activation, of p53 in ONYX-015-infected primary cells. We use a novel adenovirus mutant, ONYX-053, to demonstrate that loss of E1B-55K-mediated late viral RNA export, rather than p53 degradation, restricts ONYX-015 replication in primary cells. In contrast, we show that tumor cells that support ONYX-015 replication provide the RNA export function of E1B-55K. These data reveal that tumor cells have altered mechanisms for RNA export and resolve the controversial role of p53 in governing ONYX-015 oncolytic selectivity.

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