tetano
Editor, Senior Moderator
J Gen Virol. 2012 Oct 10. [Epub ahead of print]
THE HUMAN CATHELICIDIN, LL-37, INHIBITS INFLUENZA A VIRUSES THROUGH A MECHANISM DISTINCT FROM THAT OF SURFACTANT PROTEIN D OR DEFENSINS.
Tripathi S, Tecle T, Verma A, Crouch E, White M, Hartshorn KL.
Source
Boston University School of Medicine;
Abstract
LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and anti-fungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defense 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 mainly resulted from direct effects on the virus since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound to 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 qPCR 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 significantly to SP-D. These findings indicate that LL-37 contributes to host defense against IAV through a distinct mechanism from SP-D and HNPs.
PMID:
23052388
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23052388
THE HUMAN CATHELICIDIN, LL-37, INHIBITS INFLUENZA A VIRUSES THROUGH A MECHANISM DISTINCT FROM THAT OF SURFACTANT PROTEIN D OR DEFENSINS.
Tripathi S, Tecle T, Verma A, Crouch E, White M, Hartshorn KL.
Source
Boston University School of Medicine;
Abstract
LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and anti-fungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defense 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 mainly resulted from direct effects on the virus since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound to 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 qPCR 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 significantly to SP-D. These findings indicate that LL-37 contributes to host defense against IAV through a distinct mechanism from SP-D and HNPs.
PMID:
23052388
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23052388