Abstract:
: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(-) 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.
journal_name
J Viroljournal_title
Journal of virologyauthors
Harada JN,Berk AJdoi
10.1128/JVI.73.7.5333-5344.1999subject
Has Abstractpub_date
1999-07-01 00:00:00pages
5333-44issue
7eissn
0022-538Xissn
1098-5514journal_volume
73pub_type
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journal_title:Journal of virology
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pub_type: 杂志文章
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更新日期:1992-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.4.1244-1247.1987
更新日期:1987-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.06967-11
更新日期:2012-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.71.1.451-457.1997
更新日期:1997-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.06372-11
更新日期:2012-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.8.6155-6167.1997
更新日期:1997-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5824-5828.1995
更新日期:1995-09-01 00:00:00
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更新日期:2016-11-14 00:00:00
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更新日期:1985-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.50.3.895-903.1984
更新日期:1984-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2001-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.75.1.303-310.2001
更新日期:2001-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1982-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2014-02-01 00:00:00
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更新日期:2015-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:1976-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2020-04-16 00:00:00