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Viruses 2019, 11(1), 77; https://doi.org/10.3390/v11010077

Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1

1
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, 86000 Poitiers, France
2
Laboratoire de Virologie et Mycobactériologie, CHU de Poitiers, 86000 Poitiers, France
3
Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, BIOSIPE, 75252 Paris, France
4
Institut de Recherche pour le Développement (IRD), UMR 224 IRD-CNRS-Univ Montpellier 1 et 2 Maladies infectieuses et Vecteurs: écologie, génétique, évolution et contrôle (MiVegec), 34394 Montpellier, France
5
IRD, UMR 177 IRD-CIRAD, Interactions Hôtes-Vecteurs-Parasites-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae (InterTryp), 34394 Montpellier, France
6
Sorbonne Universités, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Eq1, 75013 Paris, France
7
AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Service de Virologie, Centre National de Référence Herpèsvirus, 75652 Paris, France
*
Author to whom correspondence should be addressed.
Received: 24 November 2018 / Revised: 15 January 2019 / Accepted: 16 January 2019 / Published: 18 January 2019
(This article belongs to the Special Issue Recent Advances of Natural Products in HSV Research)
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Abstract

Temporins are anti-microbial peptides synthesized in the skin of frogs of the Ranidae family. The few studies to date that have examined their anti-viral properties have shown that they have potential as anti-viral therapies. In this work, we evaluated the anti-herpes simplex virus type 1 (HSV-1) activity of the temporin-SHa (SHa) and its synthetic analog [K3]SHa. Human cathelicidin LL-37 and temporin-Tb (Tb), previously demonstrated to have anti-HSV-1 properties, were used as positive controls. We observed that SHa and [K3]SHa significantly inhibit HSV-1 replication in human primary keratinocytes when used at micromolar concentrations. This anti-viral activity was equivalent to that of Tb, but lower than that of LL-37. Transcriptomic analyses revealed that SHa did not act through the modulation of the cell innate immune response, but rather, displayed virucidal properties by reducing infectious titer of HSV-1 in suspension. In contrast, pre-incubation of the virus with LL-37 suggests that this peptide does not act directly on the viral particle at non-cytotoxic concentrations tested. The anti-HSV-1 activity of LL-37 appears to be due to the potentiation of cellular anti-viral defenses through the induction of interferon stimulated gene expression in infected primary keratinocytes. This study demonstrated that SHa and [K3]SHa, in addition to their previously reported antibacterial and antiparasitic activities, are direct-acting anti-HSV-1 peptides. Importantly, this study extends the little studied anti-viral attributes of frog temporins and offers perspectives for the development of new anti-HSV-1 therapies. View Full-Text
Keywords: temporin; SHa; [K3]SHa; Tb; LL-37; herpes simplex virus type 1; keratinocyte; cytotoxicity; anti-viral; immunomodulation temporin; SHa; [K3]SHa; Tb; LL-37; herpes simplex virus type 1; keratinocyte; cytotoxicity; anti-viral; immunomodulation
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Roy, M.; Lebeau, L.; Chessa, C.; Damour, A.; Ladram, A.; Oury, B.; Boutolleau, D.; Bodet, C.; Lévêque, N. Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1. Viruses 2019, 11, 77.

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