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PMID: 1851864 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

E1A represses wild-type and F9-selected polyomavirus DNA replication by a mechanism not requiring depression of large tumor antigen transcription.

Journal of virology ·Vol. 65 ·No. 6 ·1991-06-00 ·Pages 2921-8

DePolo NJ, Villarreal LP

Abstract

Polyomavirus (Py) DNA replication may be regulated to a low-level replication state in specific target cells in mice as well as in certain undifferentiated murine cell lines, such as embryocarcinoma (EC) cells. To investigate possible mechanisms by which such control may occur, we have examined the effects of E1A on Py DNA replication. Adenovirus E1A proteins repress transcriptional activation of various enhancers, including those of Py, and can stimulate DNA replication in quiescent cells, but E1A effects on Py DNA replication were unknown. We found that constitutive E1A expression in NIH 3T3 cells depressed Py DNA replication very strongly. Two F9 EC cell-selected Py enhancer variants, PyF441 and PyF101, were also examined because undifferentiated EC cells are hypothesized to have an E1A-like activity responsible for the Py restriction, and these variants activate Py DNA replication in cis in undifferentiated F9 cells. Both variants were repressed by E1A, indicating that E1A activity in 3T3 cells is not equivalent to undifferentiated F9 cell E1A-like activity. We also examined transient inducible E1A expression in cells supplying Py large tumor antigen (T-Ag). Py DNA replication was again repressed, and the inhibition increased with E1A induction. Analysis of T-Ag mRNA levels indicated that E1A repression of Py DNA replication was not an indirect result of depression of T-Ag transcription. This suggests that E1A may repress Py DNA replication by a more direct mechanism, possibly by blocking enhancer activation of DNA replication in a manner uncoupled with enhancer transcriptional control.

MeSH Terms
Adenovirus Early Proteins Animals Antigens, Viral, Tumor/genetics DNA Replication DNA, Viral/biosynthesis Enhancer Elements, Genetic Gene Expression Regulation, Viral Genetic Variation Oncogene Proteins, Viral/genetics Plasmids Polyomavirus/genetics,immunology RNA, Messenger/metabolism Repressor Proteins/genetics Transfection Tumor Cells, Cultured Virus Replication
Chemicals
Adenovirus Early Proteins Antigens, Viral, Tumor DNA, Viral Oncogene Proteins, Viral RNA, Messenger Repressor Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
DePolo N J
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Villarreal L P
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1991-06-00
Pages
2921-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240926
Subset
IM
Grants
NIGMS NIH HHS · GM 36605 · United States
NIGMS NIH HHS · GM1117702 · United States
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