Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, 86000 Poitiers, France.
Laboratoire de Virologie et Mycobactériologie, CHU de Poitiers, 86000 Poitiers, France.
Viruses. 2019 Jan 18;11(1):77. doi: 10.3390/v11010077.
Temporins are anti-microbial peptides synthesized in the skin of frogs of the 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.
瞬态蛋白是从青蛙皮肤中合成的抗菌肽。迄今为止，少数研究检查了它们的抗病毒特性，表明它们具有作为抗病毒疗法的潜力。在这项工作中，我们评估了瞬态蛋白-SHa（SHa）及其合成类似物[K³]SHa 对单纯疱疹病毒 1（HSV-1）的抑制活性。先前已证明人源抗菌肽 LL-37 和瞬态蛋白-Tb（Tb）具有抗 HSV-1 活性，被用作阳性对照。我们观察到，当使用微摩尔浓度时，SHa 和[K³]SHa 可显著抑制人原代角质形成细胞中的 HSV-1 复制。这种抗病毒活性与 Tb 相当，但低于 LL-37。转录组分析表明，SHa 不是通过调节细胞固有免疫反应起作用，而是通过降低悬浮液中 HSV-1 的感染滴度来发挥溶病毒作用。相比之下，LL-37 预先孵育病毒表明，该肽在测试的非细胞毒性浓度下不会直接作用于病毒颗粒。LL-37 的抗 HSV-1 活性似乎是由于在感染的原代角质形成细胞中诱导干扰素刺激基因表达，从而增强了细胞抗病毒防御能力。这项研究表明，SHa 和[K³]SHa 除了具有先前报道的抗细菌和抗寄生虫活性外，还是直接作用的抗 HSV-1 肽。重要的是，这项研究扩展了对青蛙瞬态蛋白研究较少的抗病毒特性，并为开发新的抗 HSV-1 疗法提供了新的视角。
