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Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. (Integrative Regenerative Medicine Centre)
Filatov Institute of Eye Diseases and Tissue Therapy, Odessa, Ukraine .
University of Aberdeen, Scotland .
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. University of Aberdeen, Scotland. (Integrative Regenerative Medicine Centre)
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2014 (English)In: Translational Vision Science & Technology, ISSN 2164-2591, Vol. 3, no 3, 1-14 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
cornea, HSV-1, antiviral peptides; nanoparticles, gene transfer
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-111486DOI: 10.1167/tvst.3.3.4PubMedID: 24932432OAI: diva2:756731
Available from: 2014-10-19 Created: 2014-10-19 Last updated: 2014-10-29Bibliographically approved

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Rajendran, VijayalakshmiPhopase, JaywantIslam, Mohammad MirazulSkog, MårtenGriffith, May
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