1. Alzheimer's disease-associated ß-amyloid does not protect against herpes simplex virus 1 infection in the mouse brain.
- Author
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Bocharova, Olga, Pandit, Narayan P., Molesworth, Kara, Fisher, Aidan, Mychko, Olga, Makarava, Natallia, and Baskakov, Ilia V.
- Subjects
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HERPES simplex virus , *VIRUS diseases , *AMYLOID beta-protein precursor , *SURVIVAL rate , *AMYLOID plaque , *ALZHEIMER'S disease , *PRESENILINS - Abstract
Alzheimer'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 ß-amyloid (Aß) 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. Seven-to ten-monthold 5XFAD animals in which extracellular Aß 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 Aß aggregates. Aß aggregates were free of HSV-1 viral particles, and the limited viral invasion to areas with a high density of Aß aggregates was attributed to phagocytic activity of reactive microglia. In the oldest mice (12-15 months old), the survival rate did not differ between 5XFAD and WT littermates. While the current study questions the antiviral role of Aß, it neither supports nor refutes the viral etiology hypothesis of late-onset AD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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