The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins.
LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and antifungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defence against influenza A virus (IAV) in recent studies. We now demonstrate dose-related neutralizing activity of LL-37 against several seasonal and mouse-adapted IAV strains. The ability of LL-37 to inhibit these IAV strains resulted mainly from direct effects on the virus, since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound high-density lipoprotein (HDL), and pre-incubation of LL-37 with human serum or HDL reduced its antiviral activity. LL-37 did not inhibit viral association with epithelial cells as assessed by quantitative RT-PCR or confocal microscopy. This finding contrasted with results obtained with surfactant protein D (SP-D). Unlike collectins or human neutrophil defensins (HNPs), LL-37 did not induce viral aggregation under electron microscopy. In the electron microscopy studies, LL-37 appeared to cause disruption of viral membranes. LL-37 had additive antiviral activity when combined with other innate inhibitors like SP-D, surfactant protein A and HNPs. Unlike HNPs, LL-37 did not bind SP-D significantly. These findings indicate that LL-37 contributes to host defence against IAV through a mechanism distinct from that of SP-D and HNPs.
Boston University School of Medicine, Department of Medicine, Boston, MA 02118, USA.
Shweta
S
Tripathi
Boston University School of Medicine, Department of Medicine, Boston, MA 02118, USA.
Tesfaldet
T
Tecle
Boston University School of Medicine, Department of Medicine, Boston, MA 02118, USA.
Anamika
A
Verma
Washington University School of Medicine, St Louis, MO 63110, USA.
Erika
E
Crouch
Boston University School of Medicine, Department of Medicine, Boston, MA 02118, USA.
Mitchell
M
White
Boston University School of Medicine, Department of Medicine, Boston, MA 02118, USA.
Kevan L
KL
Hartshorn
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000494:pharmacology*; D016466:CHO Cells; D037222:Collectins / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D023082:Defensins / Q000276:immunology / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D009980:Influenza A virus / Q000276:immunology / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000276:immunology / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology / Q000378:metabolism*; D054804:Cathelicidins
D057134:Antibodies, Neutralizing; D023181:Antimicrobial Cationic Peptides; D037222:Collectins; D023082:Defensins; D008075:Lipoproteins, HDL; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D054804:Cathelicidins