期刊论文详细信息
Frontiers in Cellular Neuroscience 卷:12
Herpes Simplex Virus Type 1 Enhances Expression of the Synaptic Protein Arc for Its Own Benefit
Patricia V. Burgos1  Carola Otth2  Mariela Muñoz4  Angara Zambrano5  Margarita I. Concha5  Paula Salazar6  Luis Leyton6  Evelyn Mancilla6  Francisca Acuña-Hinrichsen6  Carolina Martin6  Melissa Hott6 
[1] Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile;
[2] Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile;
[3] Centro de Biología Celular y Biomedicina, Facultad de Ciencia y Facultad de Medicina, Universidad San Sebastián, Santiago, Chile;
[4] Centro de Excelencia en Estudios Morfológicos y Quirúrgicos (CEMyQ), Universidad de La Frontera, Temuco, Chile;
[5] Institute of Biochemistry and Microbiology, Faculty of Science, Universidad Austral de Chile, Valdivia, Chile;
[6] Institute of Clinical Microbiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile;
[7] Institute of Physiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile;
关键词: HSV-1;    neuronal dysfunction;    Arc;    neurodegeneration;    neuronal infection;    Alzheimer’s disease;   
DOI  :  10.3389/fncel.2018.00505
来源: DOAJ
【 摘 要 】

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus able to reach the central nervous system (CNS) after primary infection in oronasal mucosa. HSV-1 establishes latency inside neurons due the repression of its gene expression process, which is related to periodic reactivations in response to cellular stress conditions, constituting a risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD). The immediate-early gene Arc plays an essential role in neuronal morphology, synaptic plasticity and memory formation. Arc acts as a hub protein, interacting with components of the endocytic machinery required for AMPA receptor (AMPAR) recycling as well as with proteins of the post-synaptic density and actin cytoskeleton. However, to date, no studies have evaluated whether persistent neurotropic HSV-1 infection modulates the expression or function of Arc protein in brain tissue. Here, we report that neuronal in vivo and in vitro infection of HSV-1 significantly increases Arc protein levels, showing a robust perinuclear distribution in neuronal cell lines, a process that is dependent on an active HSV-1 replication cycle. Finally, we found that silencing Arc protein caused a decrease in HSV-1 proteins and viral progeny, suggesting that Arc is involved in the lifecycle of HSV-1. Our studies strongly suggest that pathogenicity of HSV-1 neuronal reactivations in humans could be mediated in part by Arc neuronal upregulation and its potential role in endocytic trafficking and AMPA-neuronal function impairment. Further studies are necessary to define whether this phenomenon could have repercussions in cognition and learning processes in infected individuals.

【 授权许可】

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