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Syncytia formation affects the yield and cytotoxicity of an adenovirus expressing a fusogenic glycoprotein at a late stage of replication

Gene Therapy volume 15, pages 1240–1245 (2008)Cite this article

Abstract

Fusogenic membrane glycoproteins (FMGs) may enhance the cytotoxicity of conditionally replicative adenoviruses. However, expression at early stages of infection impairs virus replication. We have inserted the hyperfusogenic form of the gibbon ape leukemia virus (GALV) envelope glycoprotein as a new splice unit of the major late promoter (MLP) to generate a replication-competent adenovirus expressing this protein. At high multiplicity of infection (MOI), this virus replicated efficiently forming clumps of fused cells and showing a faster release. In contrast, at low MOI, infected cells formed syncytia where only one nucleus contained virus DNA, decreasing total virus production but increasing cytotoxicity.

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Acknowledgements

We thank Margarita Nadal, Eduard Serra and Jian Qiao for technical assistance. S Guedan was supported by a predoctoral fellowship (FI) granted by the Generalitat de Catalunya. AG was supported by a graduate student fellowship from Oncolytics Biotech. This work was supported by a grant from the Spanish Ministry of Education and Science, BIO2005-08682-C03-02/01 and received partial support from the Generalitat de Catalunya SGR0500008 and 200556R00066, and the Theradpox contract LSHB-CT-2005-018700 from the European Commission. RV is supported by the NIH Grant RO1CA085931.

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Author notes

  1. E Mercade and R Alemany: These authors contributed equally to this work.

Authors and Affiliations

  1. Translational Research Laboratory, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain

    S Guedan, A Gros, M Cascallo & R Alemany

  2. Department of Microbiology, University of Barcelona, Barcelona, Spain

    S Guedan & E Mercade

  3. Molecular Medicine program, Mayo Clinic, Rochester, MN, USA

    R Vile

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  1. S Guedan
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  2. A Gros
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  3. M Cascallo
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  4. R Vile
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  5. E Mercade
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  6. R Alemany
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Corresponding author

Correspondence to R Alemany.

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Guedan, S., Gros, A., Cascallo, M. et al. Syncytia formation affects the yield and cytotoxicity of an adenovirus expressing a fusogenic glycoprotein at a late stage of replication. Gene Ther 15, 1240–1245 (2008). https://doi.org/10.1038/gt.2008.94

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