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Y. Gordon, E.G. Romanowski, K.A. Yates, A.M. McDermott; Human Cathelicidin (LL–37/hCAP–18) Demonstrates Direct Antiviral Activity Against Adenovirus and Herpes Simplex Virus In Vitro. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2256.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Human cationic antimicrobial protein 18 (LL–37/hCAP–18), the only human cathelicidin described, is an effector molecule of innate immunity expressed by corneal epithelium (AM McDermott, ARVO 2003), peripheral white blood cells, and skin. Cathelicidin, is a bipartite molecule whose C–terminal domain (LL–37) has bactericidal, LPS–neutralizing, and chemotactic activity. Previous studies have demonstrated broad–spectrum antimicrobial activity against Gram–positive and Gram negative bacterial and fungal pathogens in vitro (DA Moscva, 2000), and against Pseudomonas aeruginosa in the mouse lung model in vivo (Bals, 1999). The goal of the current study was to determine whether the antimicrobial activity of LL–37 also encompasses viruses. Specifically, we tested the antiviral activity of LL–37 in a direct inhibition assay against the two most common viral ocular surface pathogens: adenovirus (Ad) (a non–enveloped virus) and herpes simplex type 1 (HSV–1) (an enveloped virus). Methods: Approximately 5 x 104 pfu of clinical isolates of Ad3, Ad5, Ad8, Ad19, and HSV–1 Mckrae were separately incubated for 4 hours at 37oC with 500 µg/ml of LL–37 or PBS. After incubation, the samples were immediately diluted 1:10 in cold tissue culture media containing 10% fetal bovine serum to inactivate the peptides. Subsequent serial dilutions were performed and aliquots plated in duplicate on A549 cells. After appropriate incubation at 37oC, the cells were stained with 0.5% gentian violet, and the plaques per well were counted under a dissecting microscope (25X) and the viral titers determined. Results: The antiviral inhibitory activities of LL–37 were expressed as the percentages of the PBS control titers after 4 hours incubation. The results for each of the virus isolates are as follows: Ad3 (72.1%); Ad5 (61.9%); Ad8 (97.0%), Ad19 (62.4%); HSV–1 Mckrae (<0.11%). Conclusions: LL–37 demonstrated significant antiviral activity against adenovirus and herpes simplex virus type 1 in a direct inhibition assay. This preliminary data suggests that the antimicrobial activity of LL–37 is broader than previously suspected and that the complexity of the ocular innate immune response to viral pathogens requires further elucidation.
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