title: Oxidative stress enhances neurodegeneration markers induced by herpes simplex virus type 1 infection in human neuroblastoma cells.
abstract: Mounting evidence suggests that Herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of Alzheimer's disease (AD). Previous work from our laboratory has shown HSV-1 infection to induce the most important pathological hallmarks of AD brains. Oxidative damage is one of the earliest events of AD and is thought to play a crucial role in the onset and development of the disease. Indeed, many studies show the biomarkers of oxidative stress to be elevated in AD brains. In the present work the combined effects of HSV-1 infection and oxidative stress on Aβ levels and autophagy (neurodegeneration markers characteristic of AD) were investigated. Oxidative stress significantly potentiated the accumulation of intracellular Aβ mediated by HSV-1 infection, and further inhibited its secretion to the extracellular medium. It also triggered the accumulation of autophagic compartments without increasing the degradation of long-lived proteins, and enhanced the inhibition of the autophagic flux induced by HSV-1. These effects of oxidative stress were not due to enhanced virus replication. Together, these results suggest that HSV-1 infection and oxidative damage interact to promote the neurodegeneration events seen in AD.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", CBMSO (UAM/CSIC), Madrid, Spain.
authors.forename: Soraya
authors.initials: S
authors.lastname: Santana
authors.forename: Isabel
authors.initials: I
authors.lastname: Sastre
authors.forename: Maria
authors.initials: M
authors.lastname: Recuero
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Bullido
authors.forename: Jesus
authors.initials: J
authors.lastname: Aldudo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006566:Herpesviridae Infections / Q000150:complications / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*