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

Autor: de Vrij J; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. R.C.Hoeben@lumc.nl, van den Hengel SK, Uil TG, Koppers-Lalic D, Dautzenberg IJ, Stassen OM, Bárcena M, Yamamoto M, de Ridder CM, Kraaij R, Kwappenberg KM, Schilham MW, Hoeben RC
Jazyk: angličtina
Zdroj: Virology [Virology] 2011 Feb 05; Vol. 410 (1), pp. 192-200. Date of Electronic Publication: 2010 Dec 04.
DOI: 10.1016/j.virol.2010.10.040
Abstrakt: 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.
(Copyright © 2010 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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