Cancer Cell
Volume 6, Issue 6, December 2004, Pages 611-623
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Article
Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity

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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.

Cited by (0)

3

These authors contributed equally to this work.

4

Present address: Genentech, Inc., 1 DNA Way, South San Francisco, California 94080

5

Present address: Chiron Corporation, 4560 Horton Street, M/S 4.1, Emeryville, California 94608

6

Present address: Guava Technologies, 25801 Industrial Boulevard, Hayward, California 94545

7

Present address: Chiron Corporation, 4560 Horton Street, M/S 4.3, Emeryville, California 94608

8

Present address: Plexxikon, Inc., 91 Bolivar Drive, Berkeley, California 94710