title: The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus.
abstract: Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there is no effective vaccine or disease modifying treatment available and novel interventions are urgently required. Cathelicidins are cationic host defence peptides expressed in the inflamed lung, with key roles in innate host defence against infection. We demonstrate that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro, retained by a truncated central peptide fragment. LL-37 prevented virus-induced cell death in epithelial cultures, significantly inhibited the production of new infectious particles and diminished the spread of infection, with antiviral effects directed both against the viral particles and the epithelial cells. LL-37 may represent an important targetable component of innate host defence against RSV infection. Prophylactic modulation of LL-37 expression and/or use of synthetic analogues post-infection may represent future novel strategies against RSV infection.
authors.affiliation: MRC Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Silke M
authors.initials: SM
authors.lastname: Currie
authors.forename: Emily Gwyer
authors.initials: EG
authors.lastname: Findlay
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McHugh
authors.forename: Annie
authors.initials: A
authors.lastname: Mackellar
authors.forename: Tian
authors.initials: T
authors.lastname: Man
authors.forename: Derek
authors.initials: D
authors.lastname: Macmillan
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Paul M
authors.initials: PM
authors.lastname: Fitch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schwarze
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology*; D014771:Virion / Q000187:drug effects / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D007370:Interferon Type I; D010446:Peptide Fragments; D054804:Cathelicidins
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