Inhibition of herpes simplex-1 virus replication by 25-hydroxycholesterol and 27-hydroxycholesterol
Valeria Cagno,
Andrea Civra,
Daniela Rossin,
Simone Calfapietra,
Claudio Caccia,
Valerio Leoni,
Nicholas Dorma,
Fiorella Biasi,
Giuseppe Poli,
David Lembo
Affiliations
Valeria Cagno
Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy
Andrea Civra
Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy
Daniela Rossin
Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy
Simone Calfapietra
Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy
Claudio Caccia
Laboratory of Clinical Pathology and Molecular Medicine, Foundation IRCCS Institute of Neurology Carlo Besta, Milano, MI, Italy
Valerio Leoni
Laboratory of Clinical Chemistry, Hospital of Varese, ASST-Settelaghi, Varese, VA, Italy
Nicholas Dorma
Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy
Fiorella Biasi
Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy
Giuseppe Poli
Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy; Corresponding authors.
David Lembo
Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy; Corresponding authors.
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. Keywords: Oxysterols, 27-hydroxycholesterol, 25-hydroxycholesterol, Herpes simplex-1, Viral inhibition, Interleukin-6
