Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy
2014 (English)In: Translational Vision Science & Technology, ISSN 2164-2591, Vol. 3, no 3, 1-14 p.Article in journal (Refereed) Published
Purpose: 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. Conclusion: 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. Translational Relevance: 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.
Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology , 2014. Vol. 3, no 3, 1-14 p.
cornea, HSV-1, antiviral peptides; nanoparticles, gene transfer
IdentifiersURN: urn:nbn:se:liu:diva-111486DOI: 10.1167/tvst.3.3.4PubMedID: 24932432OAI: oai:DiVA.org:liu-111486DiVA: diva2:756731