title: Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy.
abstract: OBJECTIVE
  To evaluate the potential utility of collagen-based corneal implants with anti-Herpes Simplex Virus (HSV)-1 activity achieved through sustained release of LL-37, from incorporated nanoparticles, as compared with cell-based delivery from model human corneal epithelial cells (HCECs) transfected to produce endogenous LL-37.
  
  
  METHODS
  We tested the ability of collagen-phosphorylcholine implants to tolerate the adverse microenvironment of herpetic murine corneas. Then, we investigated the efficacy of LL-37 peptides delivered through nanoparticles incorporated within the corneal implants to block HSV-1 viral activity. In addition, LL-37 complementary DNA (cDNA) was transferred into HCECs to confer viral resistance, and their response to HSV-1 infection was examined.
  
  
  RESULTS
  Our implants remained in herpetic murine corneas 7 days longer than allografts. LL-37 released from the implants blocked HSV-1 infection of HCECs by interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL-37 expressed and secreted the peptide. Secreted LL-37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the incidence of plaque formation and plaque size.
  
  
  CONCLUSIONS
  LL-37 released from composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both showed anti-HSV-1 activity by blocking binding. However, while both slowed down virus spread, neither was able on its own to completely inhibit the viruses.
  
  
  CONCLUSIONS
  LL-37 releasing hydrogels may have potential utility as corneal substitutes for grafting in HSV-1 infected corneas, possibly in combination with LL-37 producing therapeutic cells.
authors.affiliation: Integrative Regenerative Medicine Centre, Linköping University, Linköping, Sweden.
authors.forename: Chyan-Jang
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Eye Burns, Ophthalmic Reconstructive Surgery, Keratoplasty & Keratoprosthesis, Filatov Institute of Eye Diseases and Tissue Therapy, Odessa, Ukraine.
authors.forename: Oleksiy
authors.initials: O
authors.lastname: Buznyk
authors.affiliation: Section of Immunity, Infection and Inflammation (3I's) (Ocular Immunology), Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Kuffova
authors.affiliation: Integrative Regenerative Medicine Centre, Linköping University, Linköping, Sweden ; Section of Immunity, Infection and Inflammation (3I's) (Ocular Immunology), Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Rajendran
authors.affiliation: Section of Immunity, Infection and Inflammation (3I's) (Ocular Immunology), Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland.
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.affiliation: Integrative Regenerative Medicine Centre, Linköping University, Linköping, Sweden.
authors.forename: Jaywant
authors.initials: J
authors.lastname: Phopase
authors.affiliation: Integrative Regenerative Medicine Centre, Linköping University, Linköping, Sweden.
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Integrative Regenerative Medicine Centre, Linköping University, Linköping, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Skog
authors.affiliation: Vironova AB, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ahlqvist
authors.affiliation: Integrative Regenerative Medicine Centre, Linköping University, Linköping, Sweden.
authors.forename: May
authors.initials: M
authors.lastname: Griffith
keywords: HSV-1; antiviral peptides; nanoparticles; cornea; gene transfer