Show simple item record

dc.contributor.authorBocharova, Olga
dc.contributor.authorPandit, Narayan P
dc.contributor.authorMolesworth, Kara
dc.contributor.authorFisher, Aidan
dc.contributor.authorMychko, Olga
dc.contributor.authorMakarava, Natallia
dc.contributor.authorBaskakov, Ilia V
dc.date.accessioned2021-06-07T16:48:10Z
dc.date.available2021-06-07T16:48:10Z
dc.date.issued2021-05-28
dc.identifier.urihttp://hdl.handle.net/10713/15936
dc.description.abstractAlzheimer's disease (AD) is a devastating fatal neurodegenerative disease. An alternative to the amyloid cascade hypothesis is that a viral infection is key to the etiology of late-onset AD, with β-amyloid (Aβ) peptides playing a protective role. In the current study, young 5XFAD mice that overexpress mutant human amyloid precursor protein with the Swedish, Florida, and London familial AD mutations were infected with one of two strains of herpes simplex virus 1 (HSV-1), 17syn+ and McKrae, at three different doses. Contrary to previous work, 5XFAD genotype failed to protect mice against HSV-1 infection. The region- and cell-specific tropisms of HSV-1 were not affected by the 5XFAD genotype, indicating that host-pathogen interactions were not altered. 7- to 10-month old 5XFAD animals in which extracellular Aβ aggregates were abundant showed slightly better survival rate relative to their wild type (WT) littermates, although the difference was not statistically significant. In these 5XFAD mice, HSV-1 replication centers were partially excluded from the brain areas with high densities of Aβ aggregates. Aβ aggregates were free of HSV-1 viral particles, and the limited viral invasion to areas with a high density of Aβ aggregates was attributed to phagocytic activity of reactive microglia. In the oldest mice (12- to 15-months old), the survival rate did not differ between 5XFAD and WT littermates. While the current study questions the antiviral role of Aβ, it neither supports nor refutes the viral etiology hypothesis of late-onset AD.en_US
dc.description.urihttps://doi.org/10.1016/j.jbc.2021.100845en_US
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rightsCopyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.en_US
dc.subject5XFAD miceen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectAmyloid Precursor Proteinen_US
dc.subjectAβ aggregatesen_US
dc.subjectastrocytesen_US
dc.subjectherpes simplex virus 1en_US
dc.subjectmicrogliaen_US
dc.titleAlzheimer's disease-associated β-Amyloid does not protect against Herpes Simplex Virus 1 infection in the mouse brainen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.jbc.2021.100845
dc.identifier.pmid34052228
dc.source.beginpage100845
dc.source.endpage
dc.source.countryUnited States


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record