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Journal of Virology, January 2007, p. 954-963, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01995-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Adenoviruses Use Lactoferrin as a Bridge for CAR-Independent Binding to and Infection of Epithelial Cells{triangledown}

Cecilia Johansson,1 Mari Jonsson,1 Marko Marttila,1 David Persson,1 Xiao-Long Fan,2 Johan Skog,1 Lars Frängsmyr,3,4 Göran Wadell,1 and Niklas Arnberg1*

Departments of Virology,1 Anatomy,3 Sports Medicine, Umeå University, Umeå, Sweden,4 Department of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden2

Received 13 September 2006/ Accepted 24 October 2006

Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells and is thus not easily available to viruses. Consequently, alternative mechanisms for entry of coxsackievirus and adenovirus into cells have been suggested. We have found that tear fluid promotes adenovirus infection, and we have identified human lactoferrin (HLf) as the tear fluid component responsible for this effect. HLf alone was found to promote binding of adenovirus to epithelial cells in a dose-dependent manner and also infection of epithelial cells by adenovirus. HLf was also found to promote gene delivery from an adenovirus-based vector. The mechanism takes place at the binding stage and functions independently of CAR. Thus, we have identified a novel binding mechanism whereby adenovirus hijacks HLf, a component of the innate immune system, and uses it as a bridge for attachment to host cells.


* Corresponding author. Mailing address: Department of Virology, Umeå University, Umeå SE-90185, Sweden. Phone: 46 90 7858440. Fax: 46 90 129905. E-mail: niklas.arnberg{at}climi.umu.se.

{triangledown} Published ahead of print on 1 November 2006.


Journal of Virology, January 2007, p. 954-963, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01995-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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