title: Herpes simplex virus type 2 infection induces AD-like neurodegeneration markers in human neuroblastoma cells.
abstract: Herpes simplex virus (HSV) types 1 and 2 are neurotropic viruses that establish lifelong latent infections in neurons. Mounting evidence suggests that HSV-1 infection is involved in the pathogenesis of Alzheimer's disease (AD). The relationships between other herpesvirus infections and events associated with neurodegeneration have not, however, been extensively studied. The present work reports that HSV-2 infection leads to the strong accumulation of hyperphosphorylated tau and the amyloid-β peptides Aβ40 and Aβ42 (all major pathological hallmarks of AD) in human SK-N-MC neuroblastoma cells. Infection is also associated with a marked reduction in the amount of Aβ40 secreted and in the proteolytic fragments of the amyloid-β precursor protein (APP) (secreted APPα and the α-C-terminal fragment). These results indicate that HSV-2 infection inhibits the nonamyloidogenic pathway of APP processing and impairs Aβ secretion in these cells. In addition, HSV-2 induces the accumulation of intracellular autophagic compartments containing Aβ due to a failure in the late stages of autophagy. To our knowledge, this is the first report to show that HSV-2 infection strongly alters the tau phosphorylation state, APP processing, and autophagic process in human neuroblastoma cells, leading to the appearance of AD-like neurodegeneration markers.
authors.affiliation: Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain; Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Henrike
authors.initials: H
authors.lastname: Kristen
authors.affiliation: Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain.
authors.forename: Soraya
authors.initials: S
authors.lastname: Santana
authors.affiliation: Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain; Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto de Investigacion Sanitaria "Hospital la Paz"(IdIPaz), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sastre
authors.affiliation: Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain; Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Recuero
authors.affiliation: Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain; Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto de Investigacion Sanitaria "Hospital la Paz"(IdIPaz), Madrid, Spain. Electronic address: mjbullido@cbm.csic.es.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Bullido
authors.affiliation: Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain; Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Electronic address: jaldudo@cbm.csic.es.
authors.forename: Jesus
authors.initials: J
authors.lastname: Aldudo
mesh_terms: D000544:Alzheimer Disease / Q000821:virology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001343:Autophagy; D045744:Cell Line, Tumor; D006561:Herpes Simplex / Q000378:metabolism; D018258:Herpesvirus 2, Human; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; Amyloid-β; Autophagy; HSV-2 infection; Neurodegeneration; Tau