E1A genes of adenovirus type 2 and type 5 are expressed at different levels

E1A genes of adenovirus type 2 and type 5 are expressed at different levels Adenoviruses are an extensively studied system for modeling oncogenesis and for experimental cancer therapy. The most commonly analyzed virus types are 2 and 5, and little distinction has been made between them in past studies. Adenoviruses used for therapeutic purposes are frequently hybrids between these types, including the prototype dl 1520/Onyx015. We tested the replication of the wild-type viruses WtD (a hybrid of the type 2 E1 region and type 5) and dl 309 (type 5) in comparison with the mutants dl 1520 (hybrid) and dl 338 (type 5), the latter two lacking part of the E1B-55 kDa coding region. We found that the hybrid viruses replicated with considerably lower efficiency than their type 5 counterparts in H1299 cells ( dl 309:WtD = 3–4, dl 338: dl 1520 > 10). Moreover, adenovirus type 2 E1A expression from the hybrid viruses was strongly reduced in comparison to adenovirus type 5 E1A, as revealed by immunoblot analysis and RT-PCR, providing a potential explanation for the differences in virus yield. Differential E1A expression levels need to be taken into account for the construction of effective therapeutic viruses and when studying viral transformation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

E1A genes of adenovirus type 2 and type 5 are expressed at different levels

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Publisher
Springer-Verlag
Copyright
Copyright © 2006 by Springer-Verlag
Subject
Biomedicine; Medical Microbiology; Infectious Diseases; Virology
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-005-0702-y
Publisher site
See Article on Publisher Site

Abstract

Adenoviruses are an extensively studied system for modeling oncogenesis and for experimental cancer therapy. The most commonly analyzed virus types are 2 and 5, and little distinction has been made between them in past studies. Adenoviruses used for therapeutic purposes are frequently hybrids between these types, including the prototype dl 1520/Onyx015. We tested the replication of the wild-type viruses WtD (a hybrid of the type 2 E1 region and type 5) and dl 309 (type 5) in comparison with the mutants dl 1520 (hybrid) and dl 338 (type 5), the latter two lacking part of the E1B-55 kDa coding region. We found that the hybrid viruses replicated with considerably lower efficiency than their type 5 counterparts in H1299 cells ( dl 309:WtD = 3–4, dl 338: dl 1520 > 10). Moreover, adenovirus type 2 E1A expression from the hybrid viruses was strongly reduced in comparison to adenovirus type 5 E1A, as revealed by immunoblot analysis and RT-PCR, providing a potential explanation for the differences in virus yield. Differential E1A expression levels need to be taken into account for the construction of effective therapeutic viruses and when studying viral transformation.

Journal

Archives of VirologySpringer Journals

Published: Jun 1, 2006

References

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