title: Human cathelicidin, LL-37, inhibits respiratory syncytial virus infection in polarized airway epithelial cells.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract illness in young children worldwide. Treatment options for severe RSV disease remain limited and the development of therapeutic treatment strategies remains a priority. LL-37, a small cationic host defense peptide involved in anti-inflammatory and anti-bacterial responses, reduces replication of or infection by multiple viruses, including influenza virus, in vitro, and protects against lethal challenge with influenza virus in vivo. LL-37 also protects against RSV infection of HEp-2 cells in vitro; however, HEp-2 are not reflective of polarized airway epithelial cells and respond differently to RSV infection. An air-liquid interface (ALI) Calu-3 model that more closely mimics the human airway epithelium was established. Using this in vitro model, the effectiveness of LL-37 in preventing RSV infection and replication was examined.
  
  
  RESULTS
  LL-37, when pre-incubated with virus prior to RSV infection (prophylactic), significantly reduced the level of viral genome detected in infected Calu-3 cells, and decreased chemokine expression associated with RSV infection in vitro. In contrast, therapeutic treatment of RSV-infected ALI Calu-3 at 24 h and 3 days post-infection had minimal impact on RSV infection.
  
  
  CONCLUSIONS
  Differences in the efficacy of LL-37 at reducing RSV infection under prophylactic and therapeutic conditions may in part be ascribed to differences in the method of peptide exposure. However, the efficacy of LL-37 at reducing RSV infection under prophylactic conditions indicates that further studies examining the efficacy of LL-37 as a small peptide inhibitor of RSV are warranted.
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Gastroenteritis and Respiratory Viruses Laboratory Branch, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road NE, Mailstop A-34, Atlanta, GA, 30333, USA. zaq6@cdc.gov.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harcourt
authors.affiliation: Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, USA. il03@cdc.gov.
authors.forename: Melissa
authors.initials: M
authors.lastname: McDonald
authors.affiliation: Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, USA. hug6@cdc.gov.
authors.forename: Pavel
authors.initials: P
authors.lastname: Svoboda
authors.affiliation: Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, USA. hhe7@cdc.gov.
authors.forename: Jan
authors.initials: J
authors.lastname: Pohl
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Gastroenteritis and Respiratory Viruses Laboratory Branch, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road NE, Mailstop A-34, Atlanta, GA, 30333, USA. ket2@cdc.gov.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Tatti
authors.affiliation: National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Gastroenteritis and Respiratory Viruses Laboratory Branch, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road NE, Mailstop A-34, Atlanta, GA, 30333, USA. loh5@cdc.gov.
authors.forename: Lia M
authors.initials: LM
authors.lastname: Haynes
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D016764:Cell Polarity / Q000187:drug effects*; D018925:Chemokines / Q000378:metabolism; D017097:Electric Impedance; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology*; D006801:Humans; D008168:Lung / Q000473:pathology*; D008969:Molecular Sequence Data; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D018925:Chemokines; D054804:Cathelicidins