NP-1, a rabbit alpha-defensin, prevents the entry and intercellular spread of herpes simplex virus type 2.
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.
Sinha
Sara
S
Department of Pediatrics and Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
Cheshenko
Natalia
N
Lehrer
Robert I
RI
Herold
Betsy C
BC
D000212:Acyclovir / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D005047:Etoposide / Q000494:pharmacology; D006558:Herpes Genitalis / Q000517:prevention & control; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000378:metabolism; D014178:Translocation, Genetic / Q000187:drug effects; D014709:Vero Cells; D023084:alpha-Defensins / Q000494:pharmacology* / Q000627:therapeutic use
D000998:Antiviral Agents; C446100:NP-1 protein, Oryctolagus cuniculus; D023084:alpha-Defensins; D005047:Etoposide; D000212:Acyclovir