title: Herpes simplex virus type I induces the accumulation of intracellular β-amyloid in autophagic compartments and the inhibition of the non-amyloidogenic pathway 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). Epidemiological analyses have shown that HSV-1 is a risk factor for AD in people with at least 1 type 4 allele of the apolipoprotein E gene. Recent studies have also suggested that HSV-1 contributes to the appearance of the biochemical anomalies characteristic of AD brains. In addition, autophagic activity appears to be reduced with aging, and the final stages of autophagy in neurodegenerative process appear to be impaired. The present work reports that HSV-1 provokes the strong intracellular accumulation of both the main species of β-amyloid (Aβ) in the autophagic compartments and that it is associated with a marked inhibition of Aβ secretion. Autophagosomes containing Aβ failed to fuse with lysosomes in HSV-1-infected cells, indicating the impaired degradation of Aβ localized in the autophagic vesicles. In addition, HSV-1 infection was associated with the inhibition of the nonamyloidogenic pathway of amyloid precursor protein (APP) processing without significantly affecting the activity of the secretases involved in the amyloidogenic pathway. Taken together, these data suggest that HSV-1 infection modulates autophagy and amyloid precursor protein processing, contributing to the accumulation of Aβ characteristic of AD.
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Madrid, Spain.
authors.forename: Soraya
authors.initials: S
authors.lastname: Santana
authors.forename: Maria
authors.initials: M
authors.lastname: Recuero
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Bullido
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
authors.forename: Jesus
authors.initials: J
authors.lastname: Aldudo
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D058227:Amyloidogenic Proteins / Q000378:metabolism*; D001343:Autophagy; D045744:Cell Line, Tumor; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D058227:Amyloidogenic Proteins