alpha-Defensin inhibits influenza virus replication by cell-mediated mechanism(s).
The innate immune system mounts the first host response to pathogens. Because alpha-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 alpha-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 alpha -defensins against influenza virus. Characterizing the mechanism of action of alpha -defensins may lead to the identification of new strategies for prevention and therapy.
Salvatore
Mirella
M
Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY 100129, USA. Mirella.Salvatore@mssm.edu
Garcia-Sastre
Adolfo
A
Ruchala
Piotr
P
Lehrer
Robert I
RI
Chang
Theresa
T
Klotman
Mary E
ME
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*; D023084:alpha-Defensins / Q000276:immunology* / Q000494:pharmacology
D000998:Antiviral Agents; D014764:Viral Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D011493:Protein Kinase C