title: Use of transcriptional profiling to delineate the initial response of mice to intravaginal herpes simplex virus type 2 infection.
abstract: Intravaginal (ivag) infection of mice with herpes simplex virus type 2 (HSV-2) causes genital tissue damage, quickly followed by development of fatal encephalopathy. To delineate initial host responses generated by HSV-2 infection, here oligonucleotide microarrays compared gene expression in vaginal tissue from uninfected mice and mice 1, 2, 3, 4, 5, 6, or 7 days after ivag infection with 10(4) pfu HSV-2. While comparison of mRNA expression in uninfected and HSV-infected vaginal tissue detected few changes during the first 2 days post infection (dpi), there were 156 genes whose expression was first significantly altered 3 dpi that remained significantly modified at all later time points examined. These 156 genes were significantly enriched in canonical pathways associated with interferon (IFN) signaling, activation of IFN elements by intracellular pattern recognition receptors, and antiviral immunity induced by cytosolic RIG-like receptors. Evaluation of this gene set with the National Center for Biotechnology Information Gene and INTERFEROME databases corroborated pathway analysis, as function of most (53%) were linked to IFN-mediated host immunity. In the final set of experiments, ivag administration of the Toll-like receptor 3 agonist polyinosinic: polycytidylic acid (poly I:C) 24 h before ivag HSV-2 infection reduced the incidence of genital pathology and encephalopathy, while these poly I:C-treated mice were subsequently protected from ocular HSV-2 challenge lethal to uninfected controls. The latter results imply that the exuberant antiviral immunity produced in our experimental model is simply formed too late to prevent viral replication and dissemination, and that poly I:C-induced formation of an antiviral state protecting against primary ivag infection also permits development of HSV-specific protective immunity.
authors: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA. cherpest@pitt.edu
authors: Thomas L
authors: TL
authors: Cherpes
authors: Stephen A K
authors: SA
authors: Harvey
authors: Jaclyn M
authors: JM
authors: Phillips
authors: Rodolfo D
authors: RD
authors: Vicetti Miguel
authors: Melissa A
authors: MA
authors: Melan
authors: Nirk E
authors: NE
authors: Quispe Calla
authors: Robert L
authors: RL
authors: Hendricks
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D006558:Herpes Genitalis / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D013997:Time Factors; D014621:Vagina / Q000276:immunology / Q000473:pathology / Q000821:virology
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