Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy.

Autor: Pashaie F; Department of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the Netherlands., Hoornweg TE; Department of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the Netherlands., Bikker FJ; Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam 1081 LA, the Netherlands., Veenendaal T; Cell Microscopy Core, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584CX, the Netherlands., Broere F; Department of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the Netherlands., Veldhuizen EJA; Department of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the Netherlands. Electronic address: e.j.a.veldhuizen@uu.nl.
Jazyk: angličtina
Zdroj: Virus research [Virus Res] 2024 Dec; Vol. 350, pp. 199496. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1016/j.virusres.2024.199496
Abstrakt: Porcine epidemic diarrhea virus (PEDV) is a harmful coronavirus infecting pigs, which is resulting in substantial financial losses in the global pig industry. The lack of effective vaccines or treatments underscores the pressing need for new antiviral strategies. Antimicrobial peptides (AMPs), specifically cathelicidins such as LL-37, have demonstrated promising activity against a range of viruses. This study aims to elucidate the antiviral mechanisms of cathelicidins by examining their inhibitory capabilities against PEDV in vitro. Four pig-derived antimicrobial peptides (PMAP-36, PMAP-23, PR-39, and PG-1), together with chicken-derived CATH-B1 and human-derived LL-37 were analyzed for their anti-PEDV activity. Flow cytometry and fluorescent microscopy confirmed that LL-37 and CATH-B1 had strong inhibitory effects at non-toxic concentrations of 5 and 10 µM, significantly reducing GFP-PEDV infection of Vero cells both in co- and pre-incubation setups. In contrast, none of the porcine peptides exhibited any inhibitory effects, even at higher doses. Fluorogenic LL-37 was shown to enter VERO cells, indicative of a possible immunomodulatory antiviral mode of action. However, transmission electron microscopy clearly indicated that both LL-37 and CATH-B1 affected virus morphology and caused aggregation of viral particles, showing that peptide-virus interaction caused reduced virus infectivity. In conclusion, this analysis highlights the potential of LL-37 and CATH-B1 as inhibitors against PEDV, suggesting promising directions for innovative therapeutic antiviral strategies.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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