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 Subramanian, T.
Right arrow Articles by Chinnadurai, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Subramanian, T.
Right arrow Articles by Chinnadurai, G.

 Previous Article  |  Next Article 

Journal of Virology, February 2006, p. 2000-2012, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.2000-2012.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Genetic Identification of Adenovirus Type 5 Genes That Influence Viral Spread

T. Subramanian, S. Vijayalingam, and G. Chinnadurai*

Institute for Molecular Virology, Saint Louis University School of Medicine, 3681 Park Avenue, St. Louis, Missouri 63110

Received 28 October 2005/ Accepted 5 December 2005

The mechanisms that control cell-to-cell spread of human adenoviruses (Ad) are not well understood. Two early viral proteins, E1B-19K and E3-ADP, appear to have opposing effects since viral mutants that are individually deficient in E1B-19K produce large plaques (G. Chinnadurai, Cell 33:759-766, 1983), while mutants deficient in E3-ADP produce small plaques (A. E. Tollefson et al., J. Virol. 70:2296-2306, 1996) on infected cell monolayers. We have used a genetic strategy to identify different viral genes that influence adenovirus type 5 (Ad5) spread in an epithelial cancer cell line. An Ad5 mutant (dl327; lacking most of the E3 region) with the restricted-spread (small-plaque) phenotype was randomly mutagenized with UV, and 27 large-plaque (lp) mutants were isolated. A combination of analyses of viral proteins and genomic DNA sequences have indicated that 23 mutants contained lesions in the E1B region affecting either 19K or both 19K and 55K proteins. Four other lp mutants contained lesions in early regions E1A and E4, in the early L1 region that codes for the i-leader protein, and in late regions that code for the viral structural proteins, penton base, and fiber. Our results suggest that the requirement of E3-ADP for Ad spread could be readily compensated for by abrogation of the functions of E1B-19K and provide genetic evidence that these two viral proteins influence viral spread in opposing manners. In addition to E1B and E3 proteins, other early and late proteins that regulate viral replication and infectivity also influence lateral viral spread. Our studies have identified novel mutations that could be exploited in designing efficient oncolytic Ad vectors.

* Corresponding author. Mailing address: Institute for Molecular Virology, Saint Louis University School of Medicine, 3681 Park Avenue, St. Louis, MO 63110. Phone: (314) 977-8794. Fax: (314) 977-8798. E-mail: chinnag{at}slu.edu.

Journal of Virology, February 2006, p. 2000-2012, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.2000-2012.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dallaire, F., Blanchette, P., Groitl, P., Dobner, T., Branton, P. E. (2009). Identification of Integrin {alpha}3 as a New Substrate of the Adenovirus E4orf6/E1B 55-Kilodalton E3 Ubiquitin Ligase Complex. J. Virol. 83: 5329-5338 [Abstract] [Full Text]  
  • Leitner, S., Sweeney, K., Oberg, D., Davies, D., Miranda, E., Lemoine, N. R., Hallden, G. (2009). Oncolytic Adenoviral Mutants with E1B19K Gene Deletions Enhance Gemcitabine-induced Apoptosis in Pancreatic Carcinoma Cells and Anti-Tumor Efficacy In vivo. Clin. Cancer Res. 15: 1730-1740 [Abstract] [Full Text]  
  • Gros, A., Martinez-Quintanilla, J., Puig, C., Guedan, S., Mollevi, D. G., Alemany, R., Cascallo, M. (2008). Bioselection of a Gain of Function Mutation that Enhances Adenovirus 5 Release and Improves Its Antitumoral Potency. Cancer Res. 68: 8928-8937 [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»