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A helper-independent adenovirus vector with e1, e3, and fiber deleted: Structure and infectivity of fiberless particles

Academic Article
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Overview

authors

  • von Seggern, D. J.
  • Chiu, C. Y.
  • Fleck, S. K.
  • Stewart, P. L.
  • Nemerow, Glen

publication date

  • February 1999

journal

  • Journal of Virology  Journal

abstract

  • 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.betagal.DeltaF) with E1, E3, and L5 (fiber) deleted and analyzed the fiber null phenotype. Ad5.betagal.DeltaF 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.

subject areas

  • Adenovirus E1 Proteins
  • Adenovirus E3 Proteins
  • Adenoviruses, Human
  • Capsid
  • Capsid Proteins
  • Cell Line
  • Cell Line, Transformed
  • Gene Deletion
  • Genetic Vectors
  • Helper Viruses
  • Humans
  • Mutagenesis
  • Virion
  • beta-Galactosidase
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Identity

PubMed Central ID

  • PMC103985

International Standard Serial Number (ISSN)

  • 0022-538X

PubMed ID

  • 9882366
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Additional Document Info

start page

  • 1601

end page

  • 1608

volume

  • 73

issue

  • 2

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