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Journal of Virology, April 2009, p. 3816-3825, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02562-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells

Mari I. Jonsson, Annasara E. Lenman, Lars Frängsmyr, Cecilia Nyberg, Mohamed Abdullahi, and Niklas Arnberg^*

Division of Virology, Department of Clinical Microbiology, the Laboratory for Molecular Infection Medicine in Sweden (MIMS), Umeå University, SE-901 85 Umeå, Sweden

Received 12 December 2008/ Accepted 13 January 2009

Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on target cells in vitro, but recent research has shown that adenoviruses can also use soluble components in body fluids for indirect binding to target cells. These mechanisms have been identified upon addressing the questions of how to de- and retarget adenovirus-based vectors for human gene and cancer therapy, but the newly identified mechanisms also suggest that the role of body fluids and their components may also be of importance for natural, primary infections. Here we demonstrate that plasma, saliva, and tear fluid promote binding and infection of adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which corresponds to the natural tropism of most adenoviruses, and that plasma promotes infection by Ad31. By using a set of binding and infection experiments, we also found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just FIX, respectively, for efficient binding and infection. The concentrations of these factors that were required for maximum binding were 1/100th of the physiological concentrations. Preincubation of virions with heparin or pretreatment of cells with heparinase I indicated that the role of cell surface heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is mechanistically serotype specific. We conclude that the use of coagulation factors by adenoviruses may be of importance not only for the liver tropism seen when administering adenovirus vectors to the circulation but also during primary infections by wild-type viruses of their natural target cell types.

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* Corresponding author. Mailing address: Division of Virology, Department of Clinical Microbiology, Umeå University, SE-901 85 Umeå, Sweden. Phone: 46 90 785 8440. Fax: 46 90 12 9905. E-mail: niklas.arnberg{at}climi.umu.se

Published ahead of print on 21 January 2009.

These authors contributed equally to this work.

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Journal of Virology, April 2009, p. 3816-3825, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02562-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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