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J. Biol. Chem., Vol. 283, Issue 45, 31125-31132, November 7, 2008

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Human -Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells^*

Aisling S. Dugan, Melissa S. Maginnis, Joslynn A. Jordan, Megan L. Gasparovic^¶, Kate Manley, Rebecca Page, Geoffrey Williams, Edith Porter^||, Bethany A. O'Hara, and Walter J. Atwood¹

From the Department of Molecular Biology, Cell Biology and Biochemistry, and Graduate Program in Pathobiology, ^¶Graduate Program in Molecular & Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912 and the ^||Department of Biological Sciences, California State University, Los Angeles, California 90032

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 -defensin human neutrophil protein 1 (HNP1) and human -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.

Received for publication, July 31, 2008 , and in revised form, September 8, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants R01 CA71878 from the NCI and R01 NS43097 from the NINDS (to W. J. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Box G-E434, 70 Ship St., Providence, RI 02903. Tel.: 401-863-3116; Fax: 401-863-9653; E-mail: Walter_Atwood{at}Brown.edu.

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