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

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.