NP-1, a rabbit α-defensin, prevents the entry and intercellular spread of herpes simplex virus type 2

Sara Sinha, Natalia Cheshenko, Robert I. Lehrer, Betsy C. Herold

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Rabbit neutrophil peptide-1 (NP-1), a prototypic α-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.

Original languageEnglish (US)
Pages (from-to)494-500
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume47
Issue number2
DOIs
StatePublished - Feb 1 2003

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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