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Journal of Virology, February 2002, p. 1100-1108, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1100-1108.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Artificial Extension of the Adenovirus Fiber Shaft Inhibits Infectivity in Coxsackievirus and Adenovirus Receptor-Positive Cell Lines

Toshiro Seki, Igor Dmitriev, Elena Kashentseva, Koichi Takayama, Marianne Rots, Kaori Suzuki, and David T. Curiel*

Division of Human Gene Therapy, Departments of Medicine, Pathology, and Surgery, and the Gene Therapy Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294-3300

Received 20 September 2001/ Accepted 16 October 2001

Recent studies demonstrate that virus-cellular receptor interactions are not the sole determinants of adenovirus (Ad) tropism. It has been shown that the fiber shaft length, which ranges from 6 to 23 ß-repeats in human Ads, also influences viral tropism. However, there is no report that investigates whether artificial extension of the shaft alters the infectivity profile of Ad. Therefore, we constructed Ad serotype 5 (Ad5) capsid-based longer-shafted Ad vectors by incorporating Ad2 shaft fragments of different lengths into the Ad5 shaft. We show that "longer-shafted" Ad vectors (up to 32 ß-repeats) could be rescued. We also show that longer-shafted Ad vectors had no impact on knob-CAR (coxsackievirus and Ad receptor) interaction compared to wild-type Ad. Nevertheless, gene transfer efficiencies of longer-shafted Ad vectors were lower in CAR-positive cell lines compared to wild-type Ad. We suggest that artificial extension of the shaft can inhibit infectivity in the context of CAR-positive cell lines without modification of knob-CAR interaction.

* Corresponding author. Mailing address: Division of Human Gene Therapy, Departments of Medicine, Pathology, and Surgery, and the Gene Therapy Center, The University of Alabama at Birmingham, Birmingham, AL 35294-3300. Phone: (205) 934-8627. Fax: (205) 975-7476. E-mail: david.curiel{at}ccc.uab.edu.

Journal of Virology, February 2002, p. 1100-1108, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1100-1108.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Darr, S., Madisch, I., Hofmayer, S., Rehren, F., Heim, A. (2009). Phylogeny and primary structure analysis of fiber shafts of all human adenovirus types for rational design of adenoviral gene-therapy vectors. J. Gen. Virol. 90: 2849-2854 [Abstract] [Full Text]  
  • Excoffon, K. J. D. A., Traver, G. L., Zabner, J. (2005). The Role of the Extracellular Domain in the Biology of the Coxsackievirus and Adenovirus Receptor. Am. J. Respir. Cell Mol. Bio. 32: 498-503 [Abstract] [Full Text]  
  • Papanikolopoulou, K., Forge, V., Goeltz, P., Mitraki, A. (2004). Formation of Highly Stable Chimeric Trimers by Fusion of an Adenovirus Fiber Shaft Fragment with the Foldon Domain of Bacteriophage T4 Fibritin. J. Biol. Chem. 279: 8991-8998 [Abstract] [Full Text]  


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