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Journal of Virology, January 2009, p. 73-80, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01366-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Cationic Properties of SEVI Underlie Its Ability To Enhance Human Immunodeficiency Virus Infection

Nadia R. Roan,¹ Jan Münch,² Nathalie Arhel,² Walther Mothes,³ Jason Neidleman,¹ Akiko Kobayashi,⁴ Karen Smith-McCune,⁴ Frank Kirchhoff,² and Warner C. Greene^1,5*

Gladstone Institute of Virology and Immunology,¹ Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, California,⁵ Institute of Virology, University Clinic of Ulm, 89081 Ulm, Germany,² Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536,³ Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California⁴

Received 30 June 2008/ Accepted 10 October 2008

Human semen contains peptides capable of forming amyloid fibrils termed semen-derived enhancer of viral infection (SEVI) that can greatly increase human immunodeficiency virus (HIV) infection. While SEVI appears to enhance virion attachment to target cells, its underlying mechanism of action is unknown. We now demonstrate that the intrinsic positive charges of SEVI (pI = 10.21) facilitate virion attachment to and fusion with target cells. A mutant form of SEVI in which lysines and arginines are replaced with alanines retains the ability to form amyloid fibrils but is defective in binding virions and enhancing infection. In addition, the interaction of wild-type SEVI with virions and the ability of these fibrils to increase infection are abrogated in the presence of various polyanionic compounds. These anionic polymers also decrease the enhancement of HIV infection mediated by semen. These findings suggest that SEVI enhances viral infection by serving as a polycationic bridge that neutralizes the negative charge repulsion that exists between HIV virions and target cells. Combinations of agents that neutrale SEVI action and produce HIV virucidal effects are an attractive future direction for microbicide development.

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* Corresponding author. Mailing address: Gladstone Institute of Virology and Immunology, University of California, P.O. Box 419100, San Francisco, CA 94141-9100. Phone: (415) 695-3800. Fax: (415) 355-0855. E-mail: wgreene{at}gladstone.ucsf.edu

Published ahead of print on 22 October 2008.

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Journal of Virology, January 2009, p. 73-80, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01366-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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