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Journal of Virology, July 1999, p. 5333-5344, Vol. 73, No. 7
Molecular Biology Institute, University of
California
Received 14 January 1999/Accepted 24 March 1999
The adenovirus type 5 mutant dl1520 was engineered
previously to be completely defective for E1B-55K functions. Recently, this mutant (also known as ONYX-015) has been suggested to replicate preferentially in p53
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
p53-Independent and -Dependent Requirements for
E1B-55K in Adenovirus Type 5 Replication
Los Angeles, Los Angeles, California 90095-1570
and some p53+ tumor
cell lines but to be attenuated in primary cultured cells (C. Heise, A. Sampson-Johannes, A. Williams, F. McCormick, D. D. F. Hoff,
and D. H. Kirn, Nat. Med. 3:639-645, 1997). It has been suggested
that dl1520 might be used as a "magic bullet" that could selectively lyse tumor cells without harm to normal tissues. However, we report here that dl1520 replication is
independent of p53 genotype and occurs efficiently in some primary
cultured human cells, indicating that the mutant virus does not possess a tumor selectivity. Although it was not the sole host range
determinant, p53 function did reduce dl1520 replication
when analyzed in a cell line expressing temperature-sensitive p53
(H1299-tsp53) (K. L. Fries, W. E. Miller, and N. Raab-Traub,
J. Virol. 70:8653-8659, 1996). As found earlier for other E1B-55K
mutants in HeLa cells (Y. Ho, R. Galos, and J. Williams, Virology
122:109-124, 1982), dl1520 replication was temperature
dependent in H1299 cells. When p53 function was restored at low
temperature in H1299-tsp53 cells, it imposed a modest defect in viral
DNA replication and accumulation of late viral cytoplasmic mRNA.
However, in both H1299 and H1299-tsp53 cells, the defect in late viral
protein synthesis appeared to be much greater than could be accounted
for by the modest defects in late viral mRNA levels. We therefore
propose that in addition to countering p53 function and modulating
viral and cellular mRNA nuclear transport, E1B-55K also stimulates late
viral mRNA translation.
*
Corresponding author. Mailing address: Molecular
Biology Institute, University of California, Los Angeles, 611 Charles
Young Dr., Box 951570, Los Angeles, CA 90095-1570. Phone: (310)
206-6298. Fax: (310) 206-7286. E-mail:
berk{at}mbi.ucla.edu.
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