α-defensin inhibits influenza virus replication by cell-mediated mechanism(s)

Mirella Salvatore, Adolfo García-Sastre, Piotr Ruchala, Robert I. Lehrer, Theresa Chang, Mary E. Klotman

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Abstract

The innate immune system mounts the first host response to pathogens. Because α-defensins, which are cationic antimicrobial peptides of polymorphonuclear neutrophils and other leukocytes, are important effectors of the innate immune system, we studied the antiviral activity of human α-defensin-1 (also known as "human neutrophil peptide-1" [HNP-1]) against influenza virus in vitro. Treatment of cell cultures with HNP-1 soon after infection resulted in marked inhibition of influenza virus replication and viral protein synthesis. This effect was not due to cytotoxicity or to a direct effect on the virus. Treatment of cells with HNP-1 followed by its removal before infection also inhibited viral replication, suggesting that the inhibition was due to the modulation of cellular pathways. HNP-1 treatment inhibited protein kinase C (PKC) activation in infected cells, suggesting the involvement of the PKC pathway. Our data expand the previously known activity of α-defensins against influenza virus. Characterizing the mechanism of action of α-defensins may lead to the identification of new strategies for prevention and therapy.

Original languageEnglish (US)
Pages (from-to)835-843
Number of pages9
JournalJournal of Infectious Diseases
Volume196
Issue number6
DOIs
StatePublished - Sep 15 2007

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Salvatore, M., García-Sastre, A., Ruchala, P., Lehrer, R. I., Chang, T., & Klotman, M. E. (2007). α-defensin inhibits influenza virus replication by cell-mediated mechanism(s). Journal of Infectious Diseases, 196(6), 835-843. https://doi.org/10.1086/521027