title: Inhibition of herpes simplex-1 virus replication by 25-hydroxycholesterol and 27-hydroxycholesterol.
abstract: 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.
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cagno
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Civra
authors.affiliation: Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossin
authors.affiliation: Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Calfapietra
authors.affiliation: Laboratory of Clinical Pathology and Molecular Medicine, Foundation IRCCS Institute of Neurology Carlo Besta, Milano, MI, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Caccia
authors.affiliation: Laboratory of Clinical Chemistry, Hospital of Varese, ASST-Settelaghi, Varese, VA, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Leoni
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dorma
authors.affiliation: Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Biasi
authors.affiliation: Laboratory of General Pathology. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy. Electronic address: giuseppe.poli@unito.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.affiliation: Laboratory of Molecular Virology and Antiviral Research. Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy. Electronic address: david.lembo@unito.it.
authors.forename: David
authors.initials: D
authors.lastname: Lembo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D006888:Hydroxycholesterols; D015850:Interleukin-6; D016328:NF-kappa B; C076996:27-hydroxycholesterol; C007997:25-hydroxycholesterol
keywords: 25-hydroxycholesterol; 27-hydroxycholesterol; Herpes simplex-1; Interleukin-6; Oxysterols; Viral inhibition