Enhanced transduction of CAR-negative cells by protein IX-gene deleted adenovirus 5 vectors

Jeroen de Vrij, Sanne K. van den Hengel, Taco G. Uil, Danijela Koppers-Lalic, Iris J.C. Dautzenberg, Oscar M.J.A. Stassen, Montserrat Bárcena, Masato Yamamoto, Corrina M.A. de Ridder, Robert Kraaij, Kitty M. Kwappenberg, Marco W. Schilham, Rob C. Hoeben

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

In human adenoviruses (HAdV), 240 copies of the 14.3-kDa minor capsid protein IX stabilize the capsid. Three N-terminal domains of protein IX form triskelions between hexon capsomers. The C-terminal domains of four protein IX monomers associate near the facet periphery. The precise biological role of protein IX remains enigmatic. Here we show that deletion of the protein IX gene from a HAdV-5 vector enhanced the reporter gene delivery 5 to 25-fold, specifically to Coxsackie and Adenovirus Receptor (CAR)-negative cell lines. Deletion of the protein IX gene also resulted in enhanced activation of peripheral blood mononuclear cells. The mechanism for the enhanced transduction is obscure. No differences in fiber loading, integrin-dependency of transduction, or factor-X binding could be established between protein IX-containing and protein IX-deficient particles. Our data suggest that protein IX can affect the cell tropism of HAdV-5, and may function to dampen the innate immune responses against HAdV particles.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalVirology
Volume410
Issue number1
DOIs
StatePublished - Feb 5 2011

Bibliographical note

Funding Information:
We thank Jort Vellinga and Vivien Mautner for valuable scientific discussions and critically reading the manuscript, Steve Cramer for expert technical support, and Martijn Rabelink for producing the viruses used in these studies. This work was supported by the European Union through the 6th Framework Program GIANT (contract no. 512087 ).

Keywords

  • Adenovirus
  • Coxsackie virus and adenovirus receptor
  • Gene therapy
  • Protein IX

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