title: Human alpha-defensins inhibit BK virus infection by aggregating virions and blocking binding to host cells.
abstract: BK virus (BKV) is a polyomavirus that establishes a lifelong persistence in most humans and is a major impediment to success of kidney grafts. The function of the innate immune system in BKV infection and pathology has not been investigated. Here we examine the role of antimicrobial defensins in BKV infection of Vero cells. Our data show that alpha-defensin human neutrophil protein 1 (HNP1) and human alpha-defensin 5 (HD5) inhibit BKV infection by targeting an early event in the viral lifecycle. HD5 treatment of BKV reduced viral attachment to cells, whereas cellular treatment with HD5 did not. Colocalization studies indicated that HD5 interacts directly with BKV. Ultrastructural analysis revealed HD5-induced aggregation of virions. HD5 also inhibited infection of cells by other related polyomaviruses. This is the first study to demonstrate polyomavirus sensitivity to defensins. We also show a novel mechanism whereby HD5 binds to BKV leading to aggregation of virion particles preventing normal virus binding to the cell surface and uptake into cells.
authors.affiliation: Department of Molecular Biology, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Aisling S
authors.initials: AS
authors.lastname: Dugan
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Maginnis
authors.forename: Joslynn A
authors.initials: JA
authors.lastname: Jordan
authors.forename: Megan L
authors.initials: ML
authors.lastname: Gasparovic
authors.forename: Kate
authors.initials: K
authors.lastname: Manley
authors.forename: Rebecca
authors.initials: R
authors.lastname: Page
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Williams
authors.forename: Edith
authors.initials: E
authors.lastname: Porter
authors.forename: Bethany A
authors.initials: BA
authors.lastname: O'Hara
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Atwood
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D001739:BK Virus / Q000378:metabolism* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D006801:Humans; D027601:Polyomavirus Infections / Q000378:metabolism* / Q000473:pathology; D014709:Vero Cells; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure; D053586:Virus Internalization / Q000187:drug effects*; D023084:alpha-Defensins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; C500225:DEFA5 protein, human; D023084:alpha-Defensins; C406413:human neutrophil peptide 1
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