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Antimicrobial Agents and Chemotherapy, February 2003, p. 494-500, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.494-500.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

NP-1, a Rabbit {alpha}-Defensin, Prevents the Entry and Intercellular Spread of Herpes Simplex Virus Type 2

Sara Sinha,1 Natalia Cheshenko,1 Robert I. Lehrer,2 and Betsy C. Herold1*

Department of Pediatrics and Microbiology, Mount Sinai School of Medicine, New York, New York,1 Department of Medicine, UCLA School of Medicine, Los Angeles, California2

Received 24 June 2002/ Returned for modification 16 September 2002/ Accepted 14 November 2002

Rabbit neutrophil peptide-1 (NP-1), a prototypic {alpha}-defensin, protects cells in vitro from infection by clinical and laboratory isolates of herpes simplex virus type 2 (HSV-2). Incubation of concentrated virus stocks for 1 h with noncytotoxic concentrations of NP-1 reduces subsequent infection by >98%. Pretreating cells with NP-1 for 1 h prior to inoculation with untreated virus also prevents infection. NP-1, a cationic peptide, does not compete with viral envelope glycoproteins for binding to cellular heparan sulfate receptors, but it prevents viral entry. No VP16, a major viral tegument protein, is transported to the cell nucleus in the presence of NP-1. Infectious center assays demonstrate that NP-1 also inhibits cell-to-cell viral spread. Thus, NP-1 prevents virally mediated fusion events, entry, and cell-to-cell spread. This unique mechanism of anti-HSV activity, coupled with established antibacterial and possible anti-human immunodeficiency virus type 1 activities of defensins, render this family of compounds excellent candidates for further development as topical microbicides.

* Corresponding author. Mailing address: Pediatric Infectious Diseases, Box 1657, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029. Phone: (212) 241-6930. Fax: (212) 426-4813. E-mail: betsy.herold{at}mssm.edu.

Antimicrobial Agents and Chemotherapy, February 2003, p. 494-500, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.494-500.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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