title: Innate responses to small interfering RNA pools inhibiting herpes simplex virus infection in astrocytoid and epithelial cells.
abstract: Herpes simplex virus (HSV) is a human pathogen that can cause severe diseases such as encephalitis, keratitis and neonatal herpes. Control of HSV infection may be achieved by using small interfering (si)RNAs. We have designed and enzymatically produced pools of siRNAs targeting HSV. In addition to the target-specific effects, such siRNAs may induce innate immunity responses that may contribute to antiviral effects. HSV has versatile ways of modulating innate immunity, and it remains unclear whether HSV-specific antiviral treatment would benefit from the potential immunostimulatory effects of siRNAs. To address this, cell lines derived from epithelium and nervous system were studied for innate immunity reactions to HSV infection, to siRNA treatment, and to a combination of treatment and infection. In addition, the outcome of HSV infection was quantitated. We show that innate immunity reactions vary drastically between the cell lines. Moreover, our findings indicate only a minimal relation between the antiviral effect and the treatment-induced innate immunity responses. Thus, the antiviral effect is mainly sequence specific and the inhibition of HSV infection is not ascribed to the slight innate immunity induction.
authors.affiliation: Department of Virology, University of Turku, Turku, Finland henrik.paavilainen@utu.fi.
authors.forename: Henrik
authors.initials: H
authors.lastname: Paavilainen
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Alesia
authors.initials: A
authors.lastname: Romanovskaya
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.
authors.forename: Michaela
authors.initials: M
authors.lastname: Nygårdas
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Bamford
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Minna M
authors.initials: MM
authors.lastname: Poranen
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.
authors.forename: Veijo
authors.initials: V
authors.lastname: Hukkanen
mesh_terms: D001253:Astrocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000378:metabolism; D009928:Organ Specificity / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics; D017201:Virus Shedding / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D007370:Interferon Type I; D007372:Interferons; D007378:Interleukins; D034741:RNA, Small Interfering; D051196:Toll-Like Receptor 3; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C495344:TLR3 protein, human
keywords: Antiviral; RNA interference; herpes simplex virus; interferon; small interfering RNA