title: HSV-1-mediated modulation of cytokine gene expression in a permissive cell line: selective upregulation of IL-6 gene expression.
abstract: Pathological effects of herpes simplex virus (HSV) can result due to a combination of direct viropathic effects and immunological reactions to viral antigens. The immunological reactions are orchestrated by a variety of cytokines and chemokines released by the host cells. Therefore, the cytokine gene expression in response to HSV-1 infection in a permissive murine cell line was investigated. The data demonstrate that HSV-1 induced a selective activation of IL-6 gene expression at the mRNA and protein levels, in the permissive cell line. The cell line used was capable of expressing IL-1, IL-7, and IL-10 in addition to IL-6, upon lipopolysaccharide stimulation. UV or heat-inactivated viruses were unable to upregulate IL-6 expression. However, mutant HSV-1 strains lacking fully functional ICP0, ICP4, ICP8, or ICP27 genes, thereby rendering them replication incompetent or impaired in in vitro cell growth (ICP0), enhanced IL-6 expression selectively. Considering the role of IL-6 in inflammation, immune response, and its known association with increased levels of MyD116 and GADD 34 mRNAs (genes involved in the prevention of apoptotic death of cells), the present data may have relevance to HSV-1-mediated diseases as well as to the prevalence of HSV-1 in the host.
authors.affiliation: Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37996-0845, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kanangat
authors.forename: J S
authors.initials: JS
authors.lastname: Babu
authors.forename: D M
authors.initials: DM
authors.lastname: Knipe
authors.forename: B T
authors.initials: BT
authors.lastname: Rouse
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C057120:ICP27 protein, human herpesvirus 1; C045462:ICP8 protein, Simplexvirus; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D014764:Viral Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1