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

doi:10.1016/j.virol.2010.10.040

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

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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 language	English (US)
Pages (from-to)	192-200
Number of pages	9
Journal	Virology
Volume	410
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2010.10.040
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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de Vrij, J., van den Hengel, S. K., Uil, T. G., Koppers-Lalic, D., Dautzenberg, I. J. C., Stassen, O. M. J. A., Bárcena, M., Yamamoto, M., de Ridder, C. M. A., Kraaij, R., Kwappenberg, K. M., Schilham, M. W., & Hoeben, R. C. (2011). Enhanced transduction of CAR-negative cells by protein IX-gene deleted adenovirus 5 vectors. Virology, 410(1), 192-200. https://doi.org/10.1016/j.virol.2010.10.040

de Vrij, J, van den Hengel, SK, Uil, TG, Koppers-Lalic, D, Dautzenberg, IJC, Stassen, OMJA, Bárcena, M, Yamamoto, M, de Ridder, CMA, Kraaij, R, Kwappenberg, KM, Schilham, MW & Hoeben, RC 2011, 'Enhanced transduction of CAR-negative cells by protein IX-gene deleted adenovirus 5 vectors', Virology, vol. 410, no. 1, pp. 192-200. https://doi.org/10.1016/j.virol.2010.10.040

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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.",

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AU - Uil, Taco G.

AU - Koppers-Lalic, Danijela

AU - Dautzenberg, Iris J.C.

AU - Stassen, Oscar M.J.A.

AU - Bárcena, Montserrat

AU - Yamamoto, Masato

AU - de Ridder, Corrina M.A.

AU - Kraaij, Robert

AU - Kwappenberg, Kitty M.

AU - Schilham, Marco W.

AU - Hoeben, Rob C.

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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