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Viruses. 2019 Jan 18;11(1). pii: E77. doi: 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.

Author information

1
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, 86000 Poitiers, France. maeva.roy01@etu.univ-poitiers.fr.
2
Laboratoire de Virologie et Mycobactériologie, CHU de Poitiers, 86000 Poitiers, France. lucie.lebeau79@orange.fr.
3
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, 86000 Poitiers, France. celine.chessa@chu-poitiers.fr.
4
Laboratoire de Virologie et Mycobactériologie, CHU de Poitiers, 86000 Poitiers, France. celine.chessa@chu-poitiers.fr.
5
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, 86000 Poitiers, France. alexia.damour@univ-poitiers.fr.
6
Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, BIOSIPE, 75252 Paris, France. ali.ladram@sorbonne-universite.fr.
7
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. bruno.oury@ird.fr.
8
IRD, UMR 177 IRD-CIRAD, Interactions Hôtes-Vecteurs-Parasites-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae (InterTryp), 34394 Montpellier, France. bruno.oury@ird.fr.
9
Sorbonne Universités, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Eq1, 75013 Paris, France. david.boutolleau@aphp.fr.
10
AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Service de Virologie, Centre National de Référence Herpèsvirus, 75652 Paris, France. david.boutolleau@aphp.fr.
11
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, 86000 Poitiers, France. charles.bodet@univ-poitiers.fr.
12
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, 86000 Poitiers, France. nicolas.leveque@chu-poitiers.fr.
13
Laboratoire de Virologie et Mycobactériologie, CHU de Poitiers, 86000 Poitiers, France. nicolas.leveque@chu-poitiers.fr.

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.

KEYWORDS:

LL-37; SHa; Tb; [K3]SHa; anti-viral; cytotoxicity; herpes simplex virus type 1; immunomodulation; keratinocyte; temporin

PMID:
30669255
PMCID:
PMC6356695
DOI:
10.3390/v11010077
[Indexed for MEDLINE]
Free PMC Article

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