Elsevier

Neuroscience Letters

Volume 429, Issues 2–3, 18 December 2007, Pages 95-100
Neuroscience Letters

Herpes simplex virus infection causes cellular β-amyloid accumulation and secretase upregulation

https://doi.org/10.1016/j.neulet.2007.09.077Get rights and content

Abstract

It is uncertain whether environmental factors contribute to the formation of senile plaques and neurofibrillary tangles, the abnormal features that define the Alzheimer's disease (AD) brain. We previously proposed that herpes simplex virus type 1 (HSV1) is a strong risk factor for AD when it is present in the brains of people who possess the type 4 allele of the apolipoprotein E gene (APOE-ɛ4); however a direct biochemical link between viral infection and the development of the AD pathological features has never previously been examined. Here we show that infection of cultured neuronal and glial cells with HSV1 leads to a dramatic increase in the intracellular levels of β-amyloid (Aβ) 1–40 and 1–42, whilst levels of amyloid precursor protein (APP) in cells decrease. Similarly, Aβ1–42 deposits are present in mouse brain after HSV1 infection. In the cultured cells the mechanism involves increased Aβ production, rather than merely greater retention of cellular Aβ, as levels of β-site APP-cleaving enzyme (BACE-1) and of nicastrin, a component of γ-secretase, both increase in HSV1-infected cells. These novel data show that HSV1 can directly contribute to the development of senile plaques.

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Acknowledgements

We thank Mrs. A. Cookson for initial and Ms. A. Frost for subsequent excellent technical assistance, Prof. M. Esiri (University of Oxford) and Dr. S. Efstathiou (University of Cambridge) for HSV1-infected mouse brain sections, Dr. Marcus Hughes (Aston University) for the U87MG and T98G glioblastoma cells, Prof. N. Hooper and Dr. E. Parkin (University of Leeds) for the APP-transfected SHSY5Y neuroblastoma cells, Dr. J. Powell, Unilever Corporate Research at Sharnbrook, Beds, UK, and the

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