This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zheng, X.
Right arrow Articles by Zhou, H. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zheng, X.
Right arrow Articles by Zhou, H. S.

 Previous Article  |  Next Article 

Journal of Virology, April 2008, p. 3415-3427, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.01708-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Adenovirus E1B55K Region Is Required To Enhance Cyclin E Expression for Efficient Viral DNA Replication{triangledown}

Xinyu Zheng,1,4,{dagger} Xiao-Mei Rao,1,{dagger} Jorge G. Gomez-Gutierrez,2 Hongying Hao,2 Kelly M. McMasters,1,2 and H. Sam Zhou1,2,3*

James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky,1 Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky,2 Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky,3 Department of Surgery, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China4

Received 6 August 2007/ Accepted 9 January 2008

Adenoviruses (Ads) with E1B55K mutations can selectively replicate in and destroy cancer cells. However, the mechanism of Ad-selective replication in tumor cells is not well characterized. We have shown previously that expression of several cell cycle-regulating genes is markedly affected by the Ad E1b gene in WI-38 human lung fibroblast cells (X. Rao, et al., Virology 350:418-428, 2006). In the current study, we show that the Ad E1B55K region is required to enhance cyclin E expression and that the failure to induce cyclin E overexpression due to E1B55K mutations prevents viral DNA from undergoing efficient replication in WI-38 cells, especially when the cells are arrested in the G0 phase of the cell cycle by serum starvation. In contrast, cyclin E induction is less dependent on the function encoded in the E1B55K region in A549 and other cancer cells that are permissive for replication of E1B55K-mutated viruses, whether the cells are in the S phase or G0 phase. The small interfering RNA that specifically inhibits cyclin E expression partially decreased viral replication. Our study provides evidence suggesting that E1B55K may be involved in cell cycle regulation that is important for efficient viral DNA replication and that cyclin E overexpression in cancer cells may be associated with the oncolytic replication of E1B55K-mutated viruses.

* Corresponding author. Mailing address: University of Louisville School of Medicine, Baxter II, Room 321, 580 S. Preston St., Louisville, KY 40202. Phone: (502) 852-5745. Fax: (502) 852-2356. E-mail: hsamzhou{at}yahoo.com

{triangledown} Published ahead of print on 30 January 2008.

{dagger} These authors contributed equally to this work.

Journal of Virology, April 2008, p. 3415-3427, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.01708-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gurlevik, E., Woller, N., Schache, P., Malek, N. P., Wirth, T. C., Zender, L., Manns, M. P., Kubicka, S., Kuhnel, F. (2009). p53-dependent antiviral RNA-interference facilitates tumor-selective viral replication. Nucleic Acids Res 37: e84-e84 [Abstract] [Full Text]  
  • Blackford, A. N., Grand, R. J. A. (2009). Adenovirus E1B 55-Kilodalton Protein: Multiple Roles in Viral Infection and Cell Transformation. J. Virol. 83: 4000-4012 [Full Text]  
  • Miller, D. L., Rickards, B., Mashiba, M., Huang, W., Flint, S. J. (2009). The Adenoviral E1B 55-Kilodalton Protein Controls Expression of Immune Response Genes but Not p53-Dependent Transcription. J. Virol. 83: 3591-3603 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»