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 Jan 18;11(1):77. doi: 10.3390/v11010077.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antiviral Agents / pharmacology*
  • Anura
  • Cell Line
  • Gene Expression
  • Herpesvirus 1, Human / drug effects*
  • Humans
  • Immunity, Innate
  • Interferons / pharmacology
  • Keratinocytes / virology
  • Proteins / chemistry
  • Proteins / pharmacology*
  • Skin / chemistry*
  • Skin / cytology
  • Virus Replication / drug effects

Substances

  • Antimicrobial Cationic Peptides
  • Antiviral Agents
  • Proteins
  • temporin
  • ropocamptide
  • Interferons