Herpes Simplex Virus Type 1 Enhances Expression of the Synaptic Protein Arc for Its Own Benefit

Frontiers in Cellular Neuroscience

卷:12

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】

Unknown