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Journal of Virology, February 1999, p. 1601-1608, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
A Helper-Independent Adenovirus Vector with E1, E3, and Fiber
Deleted: Structure and Infectivity of Fiberless Particles
Dan J.
Von Seggern,1
Charles Y.
Chiu,2
Shonna Kaye
Fleck,1
Phoebe L.
Stewart,2 and
Glen R.
Nemerow1,*
Department of Immunology, The Scripps
Research Institute, La Jolla, California 92037,1
and
Department of Molecular and Medical Pharmacology and
Crump Institute for Biological Imaging, UCLA School of Medicine,
Los Angeles, California 90095-17702
Received 25 August 1998/Accepted 5 November 1998
The adenovirus (Ad) fiber protein largely determines viral tropism
through interaction with specific cell surface receptors. This molecule
may also be involved in virion assembly or maturation, as some
previously characterized fiber mutants were defective for processing of
viral structural proteins. We previously described packaging cell lines
that express Ad type 5 (Ad5) fiber and can complement the
temperature-sensitive Ad fiber mutant H5ts142. We have now
used these packaging cells to construct a new adenoviral vector
(Ad5.
gal.
F) with E1, E3, and L5 (fiber) deleted and analyzed the
fiber null phenotype. Ad5.
gal.
F growth was completely helper independent, and fiberless particles were produced by a single final
round of growth in 293 cells. Cryoelectron microscopic studies and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis
showed that the structure and composition of these particles was nearly
identical to those of first-generation Ad vectors. As expected,
fiberless particles had reduced infectivity on epithelial cells, but
they retained the ability to infect monocytic cells via an
integrin-dependent pathway. These studies provide a novel approach
to developing retargeted Ad gene therapy vectors.
*
Corresponding author. Mailing address: Department of
Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8072. Fax: (619) 784-8472. E-mail:
gnemerow{at}scripps.edu.
Journal of Virology, February 1999, p. 1601-1608, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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