title: Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells.
abstract: 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.
authors.affiliation: Department of Virology, Umeå University, Umeå, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
authors.forename: Mari
authors.initials: M
authors.lastname: Jonsson
authors.forename: Marko
authors.initials: M
authors.lastname: Marttila
authors.forename: David
authors.initials: D
authors.lastname: Persson
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Fan
authors.forename: Johan
authors.initials: J
authors.lastname: Skog
authors.forename: Lars
authors.initials: L
authors.lastname: Frängsmyr
authors.forename: Göran
authors.initials: G
authors.lastname: Wadell
authors.forename: Niklas
authors.initials: N
authors.lastname: Arnberg
mesh_terms: D000260:Adenoviruses, Human / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity*; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004847:Epithelial Cells / Q000821:virology*; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D013045:Species Specificity; D013666:Tears / Q000737:chemistry*
chemical_list: C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D007781:Lactoferrin