title: Herpes simplex virus type 1 encephalitis is associated with elevated levels of F2-isoprostanes and F4-neuroprostanes.
abstract: To better understand the pathogenesis of herpes simplex virus type 1 (HSV-1) infections of the nervous system, concentrations of F(4)-neuroprostanes (F(4)-NP) and F(2)-isoprostanes (F(2)-IP) in the murine brain were determined following intracerebral inoculation of HSV-1 or normal saline. F(4)-NP are highly selective, quantitative markers of neuronal oxidative damage, while F(2)-IP are markers of oxidative damage to brain tissue not limited to a certain cell type. In contrast to saline-treated control animals, HSV-1-infected animals developed encephalitic symptoms associated with severe inflammation, widespread HSV-1 protein expression, and significantly elevated F(4)-NP and F(2)-IP levels in the brain. Survivors of acute HSV-1 infection showed no encephalitic symptoms 2 to 3 weeks following virus inoculation. Brain tissue derived from mice euthanized 2 month after virus inoculation demonstrated expression of HSV-1 latency-associated transcripts without detectable HSV-1 protein expression. However, brain tissue from these animals showed focal chronic inflammation, moderately elevated F(2)-IP levels, and normal levels of F(4)-NP. These observations provide novel biochemical evidence that oxidant tissue injury is a mechanism underlying neuronal damage during acute HSV-1 encephalitis and suggest that oxidative damage to tissue may continue in the mammalian brain until at least several weeks after recovery from the symptomatic phase of HSV-1 infection.
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Milatovic
authors.forename: Yueli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Olson
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Montine
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
mesh_terms: D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D020803:Encephalitis, Herpes Simplex / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D028441:F2-Isoprostanes / Q000032:analysis / Q000378:metabolism*; D005260:Female; D018259:Herpesvirus 1, Human; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D014764:Viral Proteins / Q000032:analysis / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D014764:Viral Proteins