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Journal of Virology, March 1999, p. 2074-2083, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Replicative Capacities of Large E1B-Null Group
A and Group C Adenoviruses Are Independent of Host Cell p53
Status
Andrew S.
Turnell,*
Roger J. A.
Grand, and
Phillip H.
Gallimore
CRC Institute for Cancer Studies, University
of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom
Received 28 September 1998/Accepted 25 November 1998
Recent reports suggest that an early region 1B (E1B)
55,000-molecular-weight polypeptide (55K)-null adenovirus type 5 (Ad5) mutant (dl1520) can replicate to the same extent as
wild-type (wt) Ad5 in cells either deficient or mutated in p53,
implicating p53 in limiting viral replication in vivo. In contrast, we
show here that the replicative capacity of Ad5 dl1520 is
wholly independent of host cell p53 status, as is the replicative
capacity of comparable Ad12 E1B 54K-null adenoviruses (Ad12
dl620 and Ad12 hr703). Furthermore, we show
that there is no requirement for complex formation between p53 and Ad5
E1B 55K or Ad12 E1B 54K for a productive infection, such that wt Ad5
and wt Ad12 will both replicate in cells which are null for p53. In
addition, we find that these Ad5 and Ad12 mutant viruses induce S phase
irrespective of the p53 status of the cell and that, therefore, S-phase
induction does not correlate with the replicative capacity of the
virus. Interestingly, the replicative capacities of the large E1B-null
adenoviruses correlated positively with the ability to express E1B 19K
and were related to the ability to repress premature adenovirus-induced
apoptosis. Infection of primary human cells indicated that Ad5
dl1520, wt Ad5, and wt Ad12 replicated better in cycling
normal human skin fibroblasts (HSFs) than in quiescent HSFs. Thus, the
cell cycle status of the host cell, upon infection, also influences
viral yield.
*
Corresponding author. Mailing address: CRC Institute
for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom. Phone: 44-121-414 4481. Fax: 44-121-414 4486. E-mail: A.S.Turnell{at}bham.ac.uk.
Journal of Virology, March 1999, p. 2074-2083, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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