Herpes simplex virus type 2 infection induces AD-like neurodegeneration markers in human neuroblastoma cells

NEUROBIOLOGY OF AGING

卷:36

Article

Kristen, Henrike^1,2  Santana, Soraya¹  Sastre, Isabel^1,2,3  Recuero, Maria^1,2  Bullido, Maria J.^1,2,3  Aldudo, Jesus^1,2 

[1] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa CSIC UAM, E-28049 Madrid, Spain

[2] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

[3] Hosp la Paz IdIPaz, Inst Invest Sanitaria, Madrid, Spain

关键词: HSV-2 infection;    Tau;    Amyloid-beta;    Autophagy;    Neurodegeneration;    Alzheimer's disease;   

DOI  :  10.1016/j.neurobiolaging.2015.06.014

来源: Elsevier

【 摘 要 】

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-beta peptides A beta 40 and A beta 42 (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 A beta 40 secreted and in the proteolytic fragments of the amyloid-beta precursor protein (APP) (secreted APP alpha and the alpha-C-terminal fragment). These results indicate that HSV-2 infection inhibits the nonamyloidogenic pathway of APP processing and impairs A beta secretion in these cells. In addition, HSV-2 induces the accumulation of intracellular autophagic compartments containing A beta 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. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

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