Cagno Valeria, Civra Andrea, Rossin Daniela, Calfapietra Simone, Caccia Claudio, Leoni Valerio, Dorma Nicholas, Biasi Fiorella, Poli Giuseppe, Lembo David
Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
Redox Biol. 2017 Aug;12:522-527. doi: 10.1016/j.redox.2017.03.016. Epub 2017 Mar 23.
Oxysterols are known pleiotropic molecules whose antiviral action has been recently discovered. Here reported is the activity of a panel of oxysterols against HSV-1 with the identification of a new mechanism of action. A marked antiviral activity not only of 25HC but also of 27HC against HSV-1 was observed either if the oxysterols were added before or after infection, suggesting an activity unrelated to the viral entry inhibition as proposed by previous literature. Therefore, the relation between the pro-inflammatory activity of oxysterols and the activation of NF-kB and IL-6 induced by HSV-1 in the host cell was investigated. Indeed, cell pre-incubation with oxysterols further potentiated IL-6 production as induced by HSV-1 infection with a consequent boost of the interleukin's total cell secretion. Further, a direct antiviral effect of IL-6 administration to HSV-1 infected cells was demonstrated, disclosing an additional mechanism of antiviral action by both 25HC and 27HC.
氧化甾醇是已知的多效性分子，其抗病毒作用最近才被发现。本文报道了一组氧化甾醇对单纯疱疹病毒1型（HSV-1）的活性，并确定了一种新的作用机制。无论是在感染前还是感染后添加氧化甾醇，均观察到25-羟基胆固醇（25HC）和27-羟基胆固醇（27HC）对HSV-1具有显著的抗病毒活性，这表明其活性与先前文献中提出的抑制病毒进入无关。因此，研究了氧化甾醇的促炎活性与HSV-1在宿主细胞中诱导的核因子κB（NF-κB）和白细胞介素-6（IL-6）激活之间的关系。事实上，用氧化甾醇对细胞进行预孵育可进一步增强HSV-1感染诱导的IL-6产生，从而促进白细胞介素在细胞中的总分泌。此外，还证明了向HSV-1感染细胞施用IL-6具有直接抗病毒作用，揭示了25HC和27HC的另一种抗病毒作用机制。
