title: Antimicrobial peptide LL-37 attenuates infection of hepatitis C virus.
abstract: OBJECTIVE
  Although recent studies indicate that supplementation with vitamin D (VD) potentiates a sustained viral response by interferon-based therapy to chronic hepatitis C, detailed mechanisms are not fully defined. The production of cathelicidin, an antimicrobial peptide, has been demonstrated to be part of the VD-dependent antimicrobial pathway in innate immunity. Cathelicidin is known to directly kill or inhibit the growth of microbial pathogens including mycobacteria and viruses.
  
  
  METHODS
  We used a hepatitis C virus (HCV) cell culture system to clarify the anti-HCV effects of the human cathelicidin, LL-37. HuH-7 cells were administrated with LL-37 and infected with cell culture-generated HCV (HCVcc). HCV propagation was estimated by measuring the level of HCV core antigen (Ag).
  
  
  RESULTS
  Treatment with LL-37 resulted in decreased intra- and extracellular levels of HCV core Ag, suggesting inhibition of HCV propagation. To assess the effects of LL-37 on HCV replication, JFH-1 subgenomic replicon RNA-transfected cells were treated with LL-37. However, inhibition of HCV replication was not detected by this assay. To clarify the effects on HCV infection, we treated HCVcc with LL-37 and removed the antimicrobial peptide prior to use of the virus in infection. This exposure of HCVcc to LL-37 diminished the infectivity titers in a dose-dependent fashion. Iodixanol density gradient analysis revealed that the peak fraction of infectivity titer was eliminated by LL-37 treatment.
  
  
  CONCLUSIONS
  The VD-associated antimicrobial peptide LL-37 attenuated the infectivity of HCV. This anti-HCV effect of LL-37 may explain the contribution of VD to the improved efficacy of interferon-based therapy.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo.|Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo.
authors.forename: Nao
authors.initials: N
authors.lastname: Sugiyama
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo.
authors.forename: Asako
authors.initials: A
authors.lastname: Murayama
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo.
authors.forename: Norie
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology and Hepatology, Shin-Yurigaoka General Hospital, Kawasaki.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.affiliation: Division of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Asabe
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Research Institute for Gastrointestinal and Liver Diseases, Shin-Yurigaoka General Hospital, Kawasaki, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kato
keywords: cathelicidin; hepatitis C virus; interferon; vitamin D