Herpes simplex virus type 1 enhances expression of the synaptic protein arc for its own benefit

Francisca Acuña-Hinrichsen, Mariela Muñoz, Melissa Hott, Carolina Martin, Evelyn Mancilla, Paula Salazar, Luis Leyton, Angara Zambrano, Margarita I. Concha, Patricia V. Burgos, Carola Otth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Article number505
JournalFrontiers in Cellular Neuroscience
Volume12
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 Acuña-Hinrichsen, Muñoz, Hott, Martin, Mancilla, Salazar, Leyton, Zambrano, Concha, Burgos and Otth.

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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